compounds for treating cancer and other diseases

ABSTRACT

This invention provides a method of synthesizing new active compounds for pharmaceutical uses including cancer treatment, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers. This invention is an anti adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment. It modulates angiogenesis. The compounds also use as mediator of cell adhesion receptor, cell circulating, cell moving and inflammatory diseases.

This application claims priority of International App'l No. PCT/US2010/0042240, filed Jul. 16, 2010 and U.S. Ser. No. 12/856,322, filed Aug. 13, 2010. This application also claims priority of U.S. Ser. No. 12/541,713, filed Aug. 14, 2009 and claims benefit of U.S. Ser. No. 61/226,043, filed Jul. 16, 2009. This application claims priority of International App'l No. PCT/US09/34115, filed Feb. 13, 2009, This application claims benefit of U.S. Ser. No. 61/038,277 filed Mar. 20, 2008, U.S. Ser. No. 61/054,308, filed May 19, 2008, and claims priority of International App'l No. PCT/US2008/002086, filed Feb. 15, 2008, International App'l No. PCT/US2007/077273, filed Aug. 30, 2007, U.S. Ser. No. 60/890,380, filed on Feb. 16, 2007, U.S. No. 60/947,705, filed on Jul. 3, 2007, and U.S. Ser. No. 11/683,198, filed on Mar. 7, 2007, which claims benefit of U.S. Ser. Nos. 60/795,417, filed on Apr. 27, 2006, 60/841,727, filed on Sep. 1, 2006, 60/890,380, filed on Feb. 16, 2007, and International Application No. PCT/US2006/016158, filed Apr. 27, 2006, which claims the benefit of the priority of the following applications: (1) U.S. Ser. Nos. 11/289,142, filed Nov. 28, 2005, and 11/267,523, filed Nov. 4, 2005; (2) International Application No. PCT/US05/31900, filed Sep. 7, 2005 (which claims the priority of U.S. Ser. Nos. 60/617,379, filed Oct. 8, 2004, 60/613,811, filed Sep. 27, 2004, and 60/607,858, filed Sep. 7, 2004); (3) U.S. Ser. No. 11/131,551, filed May 17, 2005; and (4) U.S. Ser. No. 11/117,760, filed Apr. 27, 2005. This application also claims priority of U.S. Ser. No. 11/412,659, filed Apr. 27, 2006, U.S. Ser. No. 10/906,303, filed Feb. 14, 2005, and U.S. Ser. No. 12/344,682, filed Dec. 29, 2008. The contents of these preceding applications are hereby incorporated in their entireties by reference into this application.

FIELD OF THE INVENTION

This invention provides compounds, compositions, extracts and methods for inhibiting cancer invasion, cell invasion, or cancer cell invasion.

BACKGROUND OF THE INVENTION

This invention provides methods of synthesing new compounds for pharmaceutical uses. This invention provides methods, compounds and compositions for treating cancer, inhibiting cancer invasion, cell invasion, or cancer cell invasion, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers

SUMMARY OF THE INVENTION

This invention provides methods of synthesizing new compounds for pharmaceutical uses. This invention provides compounds, compositions, and methods for treating cancer, inhibiting cancer invasion, cell invasion, cancer cell invasion, and metastasis. This invention provides a use of compounds, compositions, for manufacturing medicament for treating cancer, inhibiting cancer invasion, and metastasis. This invention provides compounds for use as mediator or inhibitor of adhesion protein or angiopoietin, This invention provides compounds for use in a method of modulating attachment or adhesion of cells or angiogenesis, by modulating or inhibiting adhesion protein or angiopoietin, The compounds comprise the structures selected from the formulae in the present application, wherein the compounds are synthesized or isolated, wherein the compounds comprise the saponins, triterpenes, pentacyclic triterpenes, and compounds selected from formulae in the present application, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers. This invention provides compounds for use as a mediator for cell circulating, cell moving and inflammatory diseases.

DETAILED DESCRIPTION OF THE FIGURES

FIG. 1 HPLC profiles of esterification products of E4A with Tigloyl chloride (A) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature (Top row) and 0 C (bottom row).

FIG. 2 HPLC profiles of esterification products of E4A with 3,3-dimethylacryloly chloride (B) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature (Top row) and 0 C (bottom row).

FIG. 3 HPLC profiles of esterification products of E4A with 4-Pentenoyl chloride (C) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature.

FIG. 4 HPLC profiles of esterification products of E4A with Hexanoly chloride (D) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at 0C. (Top row); and shows the results of HPLC profiles of esterification products of E4A with 2-ethylbutyryl chloride (E) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at 0C.(bottom row)

FIG. 5 HPLC profiles of esterification products of E4A with Acetyl chloride (H) from different times of esterification reaction. Reaction products obtained from each time of reaction (1 min, 2 min, 5 min and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature.

FIG. 6 HPLC profiles of esterification products of E4A with Crotonoyl chloride (I) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature.

FIG. 7 HPLC profiles of esterification products of E4A with Cinnamoyl chloride (J) from different times of esterification reaction. Reaction products obtained from each time of reaction (1 min, 1 hour, 2 hours, 18 hours, 18 hours(heat)) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at Room temperature and 75C.

FIG. 8 HPLC profiles of esterification products of E4A with Benzoyl chloride (K) from different times of esterification reaction. Reaction products obtained from each time of reaction (5 sec, 1 min, 2 min, 5 min, and 10 min) were fractionated by HPLC. The profile is plotted according to HPLC elution time and optical density of fractions. Reaction was performed at 0C.

FIG. 9 MTT cytotoxic activity of times study at room temperature for A: E4A-Tigloyl; B: E4A-3,3-dimethylacryloly; C: E4A-4-pentenoyl.

FIG. 10 MTT cytotoxic activity of times study at 0C for A: E4A-Tigloyl; B: E4A-3,3-dimethylacryloly; C: E4A-4-pentenoyl.

FIG. 11 MTT cytotoxic activity of times study for J: E4A-cinnamoyl; D: E4A-hexanoyl; E: E4A-2-ethylbutyryl; and controls: Tig control is tigloyl chloride without E4A; AC control is acetyl chloride without E4A; H is acetyl chloride with E4A reaction 1 min.

FIG. 12 MTT cytotoxic activity of times study for H: E4A-acetyl; I: E4A-crotonoyl

FIG. 13 MTT cytotoxic activity of times study for E4A-Tig in 1 min, 15 min, 30 min, 1 hour, 2 hours

FIG. 14 HPLC profiles of E4A-Tig in 1 min and 2 hours

FIG. 15 MTT cytotoxic activity of times study for E4A-Tig. Results: E4A-Tigs from reaction of 5 sec to 1 min are most active. Activity decrease after 1 min of reaction. Minimum to no activity was obtained at 10 minutes or longer.

FIG. 16 Results of HPLC profiles of E4A-Tigs: E4A, E4A-ASAP (5 sec), E4A-1 min, E4A-2 min, E4A-5 min, E4A-10 min, E4A-30 min.

FIG. 17 Results of Activity order: M, N, O, P, Q, R, S, T, E4A; M=E4A has no activity.

FIG. 18 Results of MTT cytotoxic activity of E4A-Tig-R in Cancer cells of different organs: A, Bone (U2OS) IC50=4.5 ug/ml; B, Bladder (TB9): IC50=2.5 ug/ml; C, Lung (H460): IC50=4.8 ug/ml; D, Ovary (ES2): IC50=2.8 ug/ml

FIG. 19 Results of MTT cytotoxic activity of E4A-Tig-R in Cancer cells of different organs: E, Colon (HCT116) IC50=5.2 ug/ml; F, Pancreas (Capan) IC50=2.4 ug/ml; G, Ovary (OVCAR3) IC50=5.8 ug/ml; H, Breast (MCF-7) IC50=4.5 ug/ml

FIG. 20 Results of MTT cytotoxic activity of E4A-Tig-R in Cancer cells of different organs: I, Prostate (DU145) IC50=3.6 ug/ml; J, Skin (SK-Mel-5) IC 50=5.1 ug/ml; K, Mouth (KB) IC 50=3 ug/ml; L, Kidney (A498) IC 50=3.5 ug/ml

FIG. 21 Results of MTT cytotoxic activity of E4A-Tig-R in Cancer cells of different organs: M, Liver (HepG2) IC50=6 ug/ml; N, Brain (T98G) IC50=8 ug/ml; P, Leukemia (K562) IC 50=2 ug/ml; Q, Cervix (HeLa) IC 50=5 ug/ml

FIG. 22 (A) Results: Tig-N, -Q, -R, -T -S and -V do not have hemolytic activity up to 20 ug/ml. The original compound ES lyse 100% red blood cells (RBC) at 5 ug/ml. (B) Results: compare to Y3, the ACH-Y3 is less potent in hemolytic activity. Tig-R has no hemolytic activity

FIG. 23 (A) Results of HPLC profiles of reaction products. Multiple fractions were obtained. Individual fractions were collected for further studies. (B) Results of purification of E4A-Tig-R.

FIG. 24 Results of MTT assay of E4A-Tig-R with bone U2OS cell

FIG. 25 Results of HNMR of E4A-Tig-R.

FIG. 26 Results of CNMR of E4A-Tig-R.

FIG. 27 Results of HMQC of E4A-Tig-R.

FIG. 28 Results of HMBC of E4A-Tig-R.

FIG. 29 The Mass spectrum of Tig-R (M+H) is 671.4509. The mass is consistent with the proposed structure FIG. 30 The Chemical Structure of E4A-Tig-R, 24,28-O-Tigloyl-3β,16α,21β,22α,24 β,28-hexahydroxyolean-12-ene, Formular:C40H62O8, FW: 670.91548

FIG. 30 The Chemical Structure of E4A-Tig-R, 24,28-O-Tigloyl-3β,16β,21β,22α,24 β,28-hexahydroxyolean-12-ene, Formular:C40H62O8, FW: 670.91548

FIG. 31 (A) Results of HPLC profiles of reaction products. Multiple fractions were obtained. Individual fractions were collected for further studies.

(B) Results of purification of E4A-Tig-N. (C) Results of purification of E4A-Tig-S; (D) Results of purification of E4A-Tig-T.

FIG. 32 (A) Results of MTT assay of E4A-Tig-N with bone U2OS cell; (B) Results of MTT assay of E4A-Tig-S with bone U2OS cell

FIG. 33 (A) Results of MTT assay of E4A-Tig-T with bone U2OS cell; (B)shows the results of MTT assay of E4A-Tig-V with bone Ovary ES2 cell. IC50=2 ug/ml; (C) shows the results of purification of E4A-Tig-V.

FIG. 34 Results of HNMR of E4A-Tig-V.

FIG. 35 Results of HMQC of E4A-Tig-V.

FIG. 36 Results of HMBC of E4A-Tig-V.

FIG. 37 Results of Mass Spectrum of E4A-Tig-V. The Tig-R (M+H) mass is 753.4924 which is consistent with the proposed formula (C45H68O9).

DETAILED DESCRIPTION OF THE INVENTION

This invention provides a method of synthesising new active compounds for pharmaceutical uses. This invention provides an anti adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment. It modulates angiogenesis. The compounds also use as mediator of cell adhesion receptor.

This invention provides compounds or a composition comprising the compounds provided in the invention for treating cancers; for inhibiting cancer growth, for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-Kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for AntiMS, antianeurysm, antiasthmatic, anti-oedematous, anti-inflammatory, antibradykinic, anticapillarihemorrhagic, anticephalagic, anticervicobrachialgic, antieclamptic, antiedemic, antiencaphalitic, antiepiglottitic, antiexudative, antiflu, antifracture, antigingivitic, antihematomic, antiherpetic, antihistaminic, antihydrathritic, antimeningitic, antioxidant, antiperiodontic, antiphlebitic, antipleuritic, antiraucedo, antirhinitic, antitonsilitic, antiulcer, antivaricose, antivertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cancer cells, antiparasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z, and manufacturing an adjuvant composition and venotonic treatment.

This invention provides compounds, compositions and methods for treating cancer diseases, inhibiting cancer invasion, for inhibiting cancer growth or for inhibiting cancer metastasis, wherein the compounds comprise the structures selected from the formulae of the present application, wherein the compounds can be synthesized or isolated, wherein the compounds comprise the triterpenes, pentacyclic triterpenes, saponins, and compounds selected from formulae in this application, wherein the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells comprise breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell.

This invention shows that the presence of Tigloyl, angeloyl, Acetyl, Crotonoyl, 3,3-Dimethylartyloyl, senecioyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, sugar moiety, or sugar moiety substituted with diangeloyl groups, at a pentacyclic triterpene, triterpene, triterpeniod, triterpeniod saponin or compound selected from formulae of the present application, produces inhbition of cancer growth, cancer invasion, cells invasion, cancer cell invasion, cell adhesion, cell circulation or cell attachment.

This invention shows that the presence of Tigloyl, angeloyl, Acetyl, Crotonoyl, 3,3-Dimethylartyloyl, senecioyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, sugar moiety, or sugar moiety substituted with diangeloyl groups, at carbon position 21, 22, 24 and/or 28 of a pentacyclic triterpene, triterpene, triterpeniod, triterpeniod saponin or compound selected from formulae of the present application, produces inhibition of cancer growth, cancer invasion, cells invasion or cancer cell invasion. In an embodiment, the presence of group(s) selected from Tigloyl, angeloyl, Acetyl, Crotonoyl, 3,3-Dimethylartyloyl, senecioyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, and sugar moiety, at carbon position 3, 8, 15, 21, 22, 24 and/or 28 of a triterpene, triterpeniod, triterpeniod saponin or compound selected from formulae of the present application produces activities including inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion, cell adhesion, cell attachment or cell circulating. In embodiment, the presence of group at carbon position 24, produces activities. In embodiment, the presence of group at carbon position 24 and 28 produces activities. In embodiment, the presence of group at carbon position 24 and 21 produces activities. In embodiment, the presence of group at carbon position 24, 28 and 21, produces activities. In embodiment, the presence of group at carbon position 24, 28 and 22 produces activities. In embodiment, the presence of group at carbon position 24, 28 and 3 produces activities. In embodiment, the presence of group at carbon position 24, and 3 produces activities. In embodiment, the presence of group at carbon position 28 and 3 produces activities. In embodiment, the presence of group at carbon position 3 produces activities. In embodiment, the presence of group at carbon position 21 and 22 produces activities.

This invention shows a method of synthesizing active compound by attaching functional group to a core compound, wherein the functional group(s) is/are selected from tigloyl, angeloyl, acetyl, crotonoyl, 3,3-Dimethylartyloyl, senecioyl, cinnamoyl, pentenoyl, hexanoyl, benzoyl, ethylbutyryl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, and heteroraryl, wherein the core compound is a 5 ring triterpene. In embodiment, the core compound is a 4 ring terpene. In embodiment, the core compound is a 3 ring terpene. In embodiment, the core compound is a 2 ring terpene. In embodiment, the core compound is a 1 ring terpene. The compounds provided in the invention are for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating; for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-Kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for AntiMS, antianeurysm, antiasthmatic, anti-oedematous, anti-inflammatory, antibradykinic, anticapillarihemorrhagic, anticephalagic, anticervicobrachialgic, antieclamptic, antiedemic, antiencaphalitic, antiepiglottitic, antiexudative, antiflu, antifracture, antigingivitic, antihematomic, antiherpetic, antihistaminic, antihydrathritic, antimeningitic, antioxidant, antiperiodontic, antiphlebitic, antipleuritic, antiraucedo, antirhinitic, antitonsilitic, antiulcer, antivaricose, antivertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cells, antiparasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z, and manufacturing an adjuvant composition and venotonic treatment.

Experiments presented in this invention showed that the compound AKOH has no effect in inhibiting cancer growth, cancer invasion, cells invasion or cancer cell invasion. AKOH was obtained by removing the angeloyl groups from carbon positions 21 and 22 of the active Xanifolia Y(Y3). This invention shows that the ability for inhibiting cancer invasion, cells invasion or cancer cell invasion of Xanifolia Y(Y3) are lost by removing angeloyl groups from carbon positions 21 and 22.

Experiments presented in this invention showed that the core compound including E4A, E5A, Xanifolia Y-core have no effect in inhibiting cancer growth, cancer invasion, cells invasion or cancer cell invasion. Xanifolia Y-core was obtained by removing the angeloyl groups from carbon positions 21 and 22, and the sugar moieties from carbon 3 of the active Xanifolia Y(Y3). E4A (E IV A) was obtained by removing the groups from carbon positions 3, 21 and 22 of the active Escin. E5A (E V A) was obtained by removing the groups from carbon positions 3, 21 and 22 of the active Escin.

This invention showed that the core compound including E4A, E5A, Xanifolia Y-core and AKOH have no hemolytic activity and anti cancer activity.

This invention showed that Tig-N, Tig -Q, Tig-R, Tig-T Tig-S and Tig-V do not have hemolytic activity up to 20 ug/ml. The original compound ES lyse 100% red blood cells (RBC) at 5 ug/ml. Compare to Y3, the ACH-Y3 is less potent in hemolytic activity. Tig-R has no hemolytic activity. This invention showed that Tig-N, Tig -Q, Tig-R, Tig-T Tig-S and Tig-V have anti cancer activities.

This invention shows that the ability for inhibiting cancer growth, cancer invasion, cells invasion or cancer cell invasion are maintained when the sugar moieties are removed from carbon position 3 of an active compound, triterpene, triterpeniod, or triterpeniod saponin. Experiments presented in this invention showed that the compound ACH-Y3 has the ability to inhibit cancer invasion, cells invasion or cancer cell invasion. The compound ACH-Y3 was obtained by removing the sugar moieties from carbon position 3 of a active Xanifolia Y(Y3). This invention shows that the ability for inhibiting cancer invasion, cells invasion or cancer cell invasion are maintained when the sugar moieties are removed from the carbon position 3 of active Xanifolia Y(Y3).

A compound which has bio-activities including inhibiting cancer growth, inhibiting cancer invasion, cells invasion or cancer cell invasion is called active compound.

This invention provides a use for compounds, compositions, and methods for manufacturing medicament for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating, or for inhibiting cancer metastasis, wherein the compounds comprise the structures selected from the formulae of the present application, wherein the compounds can be synthesized or isolated, wherein the compounds comprise the pentacyclic triterpenes, wherein the cells comprise cancer cells, wherein the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer. The method of inhibiting cancer invasion, cells invasion or cancer cell invasion activities uses non-cytotoxic drug concentrations. The method of inhibiting metastasis uses non-cytotoxic drug concentrations. There is no noticeable change in cell morphology.

This invention provides methods for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating, migration, metastasis or growth of cancers, wherein the methods comprise affecting gene expression, wherein the methods comprise stimulating gene expression, or wherein the methods comprise inhibiting the gene expression, or wherein the methods comprise administering to a subject an effective amount of compounds, compositions in this application. In an embodiment, the method comprises contacting said cell with a compound selected from A1-18, A20-32, B1-18, B20-32, C1-18, C20-32, D1-18, D20-32, D1-18, D20-32, D1-18, D20-32, D1-18, D20-32, D1-18, D20-32, E1-18, E20-32, G1-18, G20-32, H1-18, H20-32, I1-18, I20-32, J1-18, J20-32, K1-18, K20-32, Xanifolia Y0, Y1, Y2, Y(Y3), Y5, Y7, Y8, Y9, Y10, Xanifolia (x), M10, Escin(bES), Aescin, ACH-Y(Y3), ACH-Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-Y0, ACH-X, ACH-Z4, ACH-Z1, ACH-Escin(bES), ACH-M10 and a salt, ester, metabolite thereof, and the compounds selected from formulae 2A, and K.

In vitro studies show that a compound selected from structure (2A) or (K) inhibits cell adhesion to culture flasks. The compound blocks the function of these adhesive molecules on cells. In an embodiment, the selected compound blocks the function of these adhesive molecules on cells. In an embodiment, the selected compound blocks the function of these adhesive molecules on carcinoma cells. In an embodiment, the selected compound blocks the function of these adhesive molecules on the mesothelial cells. This invention provides an anti adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment. This invention provides compounds for use as a mediator for cell circulating, cell moving and inflammatory diseases. In an embodiment, the selected compound binds to the adhesive proteins (by masking) on the membrane and inhibits the interaction of adhesion proteins with their receptors. In an embodiment, the selected compound's action on the membrane affects adhesion proteins' function in the membrane. The lost of adhesion activity of cancer cells is result from direct or indirect action of the selected compound on membrane proteins.

(Our purification methods and biological assays include the MTT assay in International Application No. PCT/US05/31900, filed Sep. 7, 2005, U.S. Ser. No. 11/289,142, filed Nov. 28, 2005, and U.S. Ser. No. 11/131,551, filed May 17, 2005, and PCT/US2008/002086, 1188-ALA-PCT, filed Feb. 15, 2008, the cell invasion experiments methods in International Application PCT/US2010/0042240, filed Jul. 16, 2010, the contents of which are incorporated herein by reference)

This invention provides a use of compounds or methods for inhibiting cancer invasion, cell invasion, cancer cell invasion, migration, metastasis or growth of cancers, wherein this invention comprises a process and method for administration of the composition, wherein administration is by intravenous injection, intravenous drip, intraperitoneal injection or oral administration; wherein administration is by intravenous drip: 0.003-0.03 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.003-0.03 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution, or 0.01-0.03 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.01-0.03 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution, or 0.01-0.05 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.01-0.05 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution, or 0.05-0.2 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.05-0.2 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution, or by intravenous drip: 0.1-0.2 mg/kg body weight per day of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.1-0.2 mg/kg body weight per day compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution, or by intraperitoneal injection(I.P.): 2.5 mg/kg body weight per day compound dissolved in 10% glucose solution or of 0.9% NaCl solution, or by oral administration wherein the dosage of mammal is 1-10 mg/kg, 10-30 mg/kg, 30-60 mg/kg, or 60-90 mg/kg body weight of compound, or by intravenous injection or intravenous drip wherein the dosage of mammal is 0.01-0.1 mg/kg body weight, 0.1-0.2 mg/kg, 0.2-0.4 mg/kg body weight, or 0.4-0.6 mg/kg body weight of compound, or by intraperitoneal injection (I.P.) wherein the dosage of mammal is 1-3 mg/kg, 3-5 mg/kg, 4-6 mg/kg, or 6-10 mg/kg body weight of compound.

This invention provides a use of compounds or methods for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating, migration, metastasis or growth of cancers, wherein the invention comprises a pharmaceutical composition comprising the compound of this invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein said compound is present in a concentration of 0.01 ug/ml to 65 ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 40 ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 8 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 9 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 8 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 9 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 30 ug/ml.

This invention provides a use of compounds or methods for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating, migration, metastasis or growth of cancers, wherein the invention comprises a pharmaceutical composition comprising the compound of this invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent, wherein said compound is present in a concentration of 0.008 uM to 80 uM, or wherein said compound is present in a concentration of 0.01 uM to 60 uM, or wherein said compound is present in a concentration of 0.01 uM to 50 uM, or wherein said compound is present in a concentration of 0.01 uM to 40 uM, or wherein said compound is present in a concentration of 0.01 uM to 30 uM, or wherein said compound is present in a concentration of 0.01 uM to 20 uM, or wherein said compound is present in a concentration of 0.01 uM to 10 uM, or wherein said compound is present in a concentration of 5 uM to 10 uM, or wherein said compound is present in a concentration of 0.1 uM to 5 uM, or wherein said compound is present in a concentration of 0.1 uM to 7.5 uM, or wherein said compound is present in a concentration of 0.1 uM to 10 uM, or wherein said compound is present in a concentration of 0.1 uM to 15 uM, or wherein said compound is present in a concentration of 0.1 uM to 20 uM, or wherein said compound is present in a concentration of 0.1 uM to 30 uM or wherein said compound is present in a concentration of 0.1 uM to 40 uM, or wherein said compound is present in a concentration of 0.1 uM to 50 uM or wherein said compound is present in a concentration of 0.1 uM to 60 uM, or wherein said compound is present in a concentration of 0.1 uM to 80 uM, or wherein said compound is present in a concentration of 1 uM to 5 uM, or wherein said compound is present in a concentration of 1 uM to 7.5 uM, or wherein said compound is present in a concentration of 1 uM to 10 uM, or wherein said compound is present in a concentration of 1 uM to 15 uM, or wherein said compound is present in a concentration of 1 uM to 20 uM, or wherein said compound is present in a concentration of 1 uM to 30 uM or wherein said compound is present in a concentration of 1 uM to 40 uM, or wherein said compound is present in a concentration of 1 uM to 50 uM or wherein said compound is present in a concentration of 1 uM to 60 uM, or wherein said compound is present in a concentration of 1 uM to 80 uM, or wherein said compound is present in a concentration of 3 uM to 5 uM, or wherein said compound is present in a concentration of 3 uM to 7.5 uM, or wherein said compound is present in a concentration of 3 uM to 10 uM, or wherein said compound is present in a concentration of 3 uM to 15 uM, or wherein said compound is present in a concentration of 3 uM to 20 uM, or wherein said compound is present in a concentration of 3 uM to 30 uM or wherein said compound is present in a concentration of 3 uM to 40 uM, or wherein said compound is present in a concentration of 3 uM to 50 uM or wherein said compound is present in a concentration of 3 uM to 60 uM, or wherein said compound is present in a concentration of 3 uM to 80 uM, or wherein said compound is present in a concentration of 5 uM to 8 uM, or wherein said compound is present in a concentration of 5 uM to 10 uM, or wherein said compound is present in a concentration of 5 uM to 15 uM, or wherein said compound is present in a concentration of 5 uM to 20 uM, or wherein said compound is present in a concentration of 5 uM to 30 uM or wherein said compound is present in a concentration of 5 uM to 40 uM, or wherein said compound is present in a concentration of 5 uM to 50 uM or wherein said compound is present in a concentration of 5 uM to 60 uM, or wherein said compound is present in a concentration of 5 uM to 80 uM. or wherein said compound is present in a concentration of 7 uM to 8 uM, or wherein said compound is present in a concentration of 7 uM to 10 uM, or wherein said compound is present in a concentration of 7 uM to 15 uM, or wherein said compound is present in a concentration of 7 uM to 20 uM, or wherein said compound is present in a concentration of 7 uM to 30 uM or wherein said compound is present in a concentration of 7 uM to 40 uM, or wherein said compound is present in a concentration of 7 uM to 50 uM or wherein said compound is present in a concentration of 7 uM to 60 uM, or wherein said compound is present in a concentration of 7 uM to 80 uM.

The invention will be better understood by reference to the Experimental Details which follow, but those skilled in the art will readily appreciate that the specific experiments detailed are only illustrative, and are not meant to limit the invention as described herein, which is defined by the claims which follow thereafter.

Throughout this application, various references or publications are cited. Disclosures of these references or publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.

It is to be noted that the transitional term “comprising”, which is synonymous with “including”, “containing” or “characterized by”, is inclusive or open-ended and does not exclude additional, un-recited elements or method steps.

Example 1 Tablet for Dose Containing 10 mg, 20 mg 30 mg of Active Compound

Active 1 mg 5 mg 10 mg 20 mg 30 mg compound Microcrys- 20 mg 20 mg 19.75 mg 60 mg 100 mg talline cellulose Corn starch 29 mg 24.5 mg 19.75 mg 19.25 mg 18.5 mg Magnesium 0 mg 0.5 mg 0.5 mg 0.75 mg 1.5 mg stearate

The active compound, cellulose, and a portion of the corn starch are mixed and granulated to 10% corn starch paste. The resulting granulation is sieved, dried and blended with the remainder of the corn starch and the magnesium stearate. The resulting granulation is then compressed into tablets containing 1, 5, 10, 20, 30 mg, respectively of active ingredient per tablet.

Example 2 Intravenous Solution Preparation

An intravenous dosage form of the active compound is prepared as follows:

Active compound 1-10 ug Sodium citrate 5-50 mg Citric acid 1-15 mg Sodium chloride 1-8 mg Water for injection (USP) q.s. to 1 mL

Utilizing the above quantities, the active compound is dissolved at room temperature in a prepared solution of sodium chloride, citric acid, and sodium citrate in water for injection.

Example 3 Intravenous Drip Preparation

0.25-2.5 mg compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution.

Intravenous drip preparation: 1-2.mg compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution

Treatment of angelic acid with one of the many standard chlorinating reagents including phosphorus ocychloride, phosphorus trichloride and thionyl chloride produces tigloyl chloride. Oxalyl chloride produces a 2:1 ratio of angeloyl chloride to tigloyl chloride. Treatment of potassium salt in diethyl ether with oxalyl chloride and catalytic DMF for 2 hr at 0C produces pure angeloyl chloride.

Acid Hydrolysis of the Following Compounds: a) Xanifolia(Y),

or chemical name: 3-O-[β-D-galactopyranosyl (1→2)]-α-L-arabinofuranosy (1→3)-β-D-glucuronopyranosyl-21,22-O-diangeloyl-3β,15α,16α,21β,22α,28-hexahydroxyolean-12-ene;

c) Xanifolia (Y2),

or chemical name: 3-O[β-D-glucopyranosyl-(1→2)]-α-L-arabinofuranosy (13→)-β-D-glucuronopyranosyl-21,22-O-diangeloyl-3β,15α,16α,21β,22α,24β,28-heptahydroxyolean-12-ene;

d) Xanifolia (Y8),

or chemical name: 3-O-[β-glucopyranosyl (1→2)]-α-arabinofuranosyl (1→3)-β-glucuronopyranosyl-21,22-O-diangeloyl-3β,16α,21β,22α,24β,28-hexahydroxyolean-12-ene;

f) Xanifolia (Y10),

or chemical name: 3-O-[β-galactopyranosyl (1→2)]-α-arabinofuranosyl (1→3)-β-glucuronopyranosyl-21,22-O-diangeloyl-3β,16α,21β,22α,28-pentahydroxyolean-12-ene. j) structure (M10)

m) structure (bES):

After acid hydrolysis of the above, an isolated, purified or synthesized compound is produced having a structure (ACH) selected from following:

The composition comprises bioactive compounds from natural plants or synthesis. The program is based on our purification methods and biological assays including the MTT assay. See International Application No. PCT/US05/31900, filed Sep. 7, 2005, U.S. Ser. No. 11/289,142, filed Nov. 28, 2005, and U.S. Ser. No. 11/131,551, filed May 17, 2005, and PCT/US2008/002086, 1188-ALA-PCT, filed Feb. 15, 2008, Ser. No. 12/344,682,1020-B1-US, filed Dec. 29, 2008, the contents of which are incorporated herein by reference. The details of Analysis of gene expression of ES2 cells after Y-treatment by Microarray, Data Analysis Methods and Western blot in PCT/US2008/002086, 1188-ALA-PCT, filed Feb. 15, 2008, and the cell invasion experiments methods in International Application PCT/US2010/0042240, filed Jul. 16, 2010, the contents of which are incorporated herein by reference.

The Haemolytic Assay

Erythrocytes (RBC) were isolated from human blood (EDTA whole blood, collected randomly). 50 ul of the 10% RBC suspension (in PBS) was added to 2 ml of sample solutions (concentration range from 0.1 ug/ml to 400 ug/ml) in PBS. The mixture was vortexed briefly and sat for 60 min at room temperature. The mixture was spun at 3K for 10 min and the relative amounts of lysed hemoglobin in the supernatant were measured at 540 nm. The synthetic compounds of present application were tested with this method.

Acid Hydrolysis of Saponin

15 mg Xanifolia-Y was dissolved in 1 ml of methanol. 1 ml of 2N HCl was then added. The mixture was refluxed in 80C water bath for 5 hours. The solution was then neutralized by adding 2 ml of 1N NaOH (to final pH 4-6). The aglycone was then extracted with ethylacetate 3 ml×2. The extracts were collected and pooled. Further isolation of aglycone (ACH-Y) was achieved by HPLC with isocratic elution of 80-100% acetonitrile. Repeating the experiment with compounds Z4, Y10, Y2, Y8, Y7, Y0, X, M10 and ESCIN(bES) gives the following compounds respectively: ACH-Z4, ACH-Y10, ACH-Y2, ACH-Y8, ACH-Y7, ACH-Y0, ACH-X, ACH-E, ACH-Z5, ACH-M10 and ACH-bES. Experiments methods in International Application PCT/US2010/0042240, filed Jul. 16, 2010, the contents of which are incorporated herein by reference.

Removal of the Acyl Group by Alkaline Hydrolysis

20 mg of Xanifolia-Y was dissolved in 0.5 ml of 1N NaOH. The solution was incubated in 80C water bath for 4 hours. It was cooled to room temperature before being neutralized with 0.5 ml 1N HCl (adjust pH to about 3). The mixture was extracted with 2 ml 1-butanol 3 times. The butanol fractions were collected and lyophilized. The hydrolyzed saponin was further purified with HPLC in a C-18 column eluted with 25% acetonitrile.

Compounds AKOH-Y and AKOH-M10 do not show the ability to inhibit cancer growth, cancer invasion, cells invasion or cancer cell invasion.

Core Compound

A core compound or pentacyclic triterpenes, hydroxylated triterpenes is obtained by acid and alkaline hydroysis of saponin from natural sources. A pentacyclic triterpene can also be obtained by synthetic methods. A method for synthesizing the core compound is as follows:

Beta-Escin, compound Y, Y10, Y2, Y8, Y7, Y0, X, or M10 dissolved in 1M NaOH (20 mg/ml) was incubated at 70C for 5 hours. The hydrolyzed solution was neutralized with HCl and the water was evaporated by lyophilization. The product was dissolved in 50% methanol and 1N HCl. The mixture was incubated at 70C for 5 hours. The solution was neutralized with NaOH. The hydrolyzed product was extracted with ethylacetate, which was subsequently removed by evaporation. Further purification of the hydrolyzed product of core compounds including (E4A) were archived with FPLC chromatography in a C18 column equilibrated with 70% acetonitrile/TFA at the flow rate of 1 ml/min. The core compounds are obtained.

The core compounds do not show the ability to inhibit cancer growth, cancer invasion, or cell adhesion.

The structures of core compounds:

wherein R1, R2, R5, R8 represent OH; R3 represents OH, H or absent; R4, R10 represent CH3 or CH2OH; R9, R11, R12, R13, R14, R15 represent CH3;

wherein R1, R2, R5, R8, R17, R18 represent OH; R3 represents OH, H or absent; R9, R11, R12, R13, R14, R15 represent CH3.

A typical numbering 1 to 30 of carbon positions of a pentacyclic triterpene.

wherein R1, R2, R5, R8, R17, R18 represent OH; R9, R11, R12, R13, R14, R15 represent CH3, also named E4A or (E).

This invention provides a method of synthesizing new active compounds. A method of attaching functional groups to the core compounds [including but not limited to (A), (B), (C), (D), (E), (F), (G), (H)] involves esterification of core compounds with acyl chloride including but not limited to Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride or Ethylbutyryl chloride for 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at 0C, 25C or 75C temperature. At the end of reaction, 5 ml of 2N HCl or 1M NaHCO3 is added to the reaction mixture. The solution is then extracted 3 times with 10 ml of ethyl acetate which is then evaporated under vacuum and at 45C and lyophilization. The reaction product is dissolved in 80% acetonitrile—0.005% Trifluoroacetic acid. The active esterification products are purified with HPLC. MTT activity was performed to test the activity of acyl chloride, solution after the reaction, individual fractions, and individual compounds. The core compounds are synthetic, semi synthetic or from natural source. The core compounds are including terpene, isoprene, triterpenes, and hydroxylated triterpenes.

MTT activity of acylation of core compounds in different reaction time period of (ASAP)5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at 0C, 25C or 75C temperature were studied. HPLC profiles of esterification products of core compound E4A with acyl chloride including tigloyl chloride, angeloyl chloride, acetyl chloride, crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, cinnamoyl chloride, pentenoyl chloride, hexanoyl chloride, benzoyl chloride or ethylbutyryl chloride show that the compounds vary in composition when the time or temperature of the reaction is changed. See FIGS. 1-21

The peaks, fractions and compounds are selected according to the activities of times studies and the changes of peaks. Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific time. The compounds having strong to weak activities are selected and isolated. The anti cancer activities are the MTT studies of bone (U2OS), lung (H460), bladder(HTB-9), ovary (ES2), colon (HCT116), pancreas (Capan), ovary(OVCAR3), prostate (DU145), skin (SK-Mel-5), mouth (KB), kidney (A498), breast (MCF-7), liver (HepG2), brain (T98G), luekemia (K562), cervix (HeLa).

Esterification of core compound E4A with Tigloyl chloride and isolation of the compounds with HPLC give the following compounds:

R1 R2 R5 R8 R17 R18 Cytotoxicity activity E4A OH OH OH OH OH OH none A1 OH OH OH OH O-Tig OH moderate A2 OH OH OH OH OH O-Tig moderate A3 OH OH OH OH O-Tig O-Tig strong A4 O-Tig OH OH OH O-Tig O-Tig moderate A5 OH O-Tig OH OH O-Tig O-Tig moderate A6 OH OH O-Tig OH O-Tig O-Tig moderate A7 OH OH OH O-Tig O-Tig O-Tig moderate A8 O-Tig O-Tig OH OH O-Tig O-Tig weak A9 OH O-Tig O-Tig OH O-Tig O-Tig weak A10 OH OH O-Tig O-Tig O-Tig O-Tig weak A11 O-Tig OH O-Tig OH O-Tig O-Tig weak A12 OH O-Tig OH O-Tig O-Tig O-Tig weak A13 O-Tig OH OH O-Tig O-Tig O-Tig weak A14 OH O-Tig O-Tig OH O-Tig O-Tig weak A15 O-Tig O-Tig O-Tig OH O-Tig O-Tig weak A16 O-Tig O-Tig OH O-Tig O-Tig O-Tig weak A17 O-Tig OH O-Tig O-Tig O-Tig O-Tig weak A18 OH O-Tig O-Tig O-Tig O-Tig O-Tig weak A19 O-Tig O-Tig O-Tig O-Tig O-Tig O-Tig none A20 O-Tig O-Tig OH OH OH O-Tig moderate A21 O-Tig O-Tig OH OH O-Tig OH moderate A22 O-Tig O-Tig OH O-Tig OH OH moderate A23 O-Tig O-Tig O-Tig OH OH OH moderate A24 O-Tig O-Tig OH OH OH OH moderate A25 O-Tig OH OH OH OH O-Tig moderate A26 OH O-Tig OH OH OH O-Tig moderate A27 OH OH O-Tig OH OH O-Tig moderate A28 OH OH OH O-Tig OH O-Tig moderate A29 O-Tig OH OH OH O-Tig OH moderate A30 OH O-Tig OH OH O-Tig OH moderate A31 OH OH O-Tig OH O-Tig OH moderate A32 OH OH OH O-Tig O-Tig OH moderate

Esterification of core compound E4A with Angeloyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A OH OH OH OH OH OH none G1 OH OH OH OH O-Ang OH moderate G2 OH OH OH OH OH O-Ang moderate G3 OH OH OH OH O-Ang O-Ang strong G4 O-Ang OH OH OH O-Ang O-Ang moderate G5 OH O-Ang OH OH O-Ang O-Ang moderate G6 OH OH O-Ang OH O-Ang O-Ang moderate G7 OH OH OH O-Ang O-Ang O-Ang moderate G8 O-Ang O-Ang OH OH O-Ang O-Ang weak G9 OH O-Ang O-Ang OH O-Ang O-Ang weak G10 OH OH O-Ang O-Ang O-Ang O-Ang weak G11 O-Ang OH O-Ang OH O-Ang O-Ang weak G12 OH O-Ang OH O-Ang O-Ang O-Ang weak G13 O-Ang OH OH O-Ang O-Ang O-Ang weak G14 OH O-Ang O-Ang OH O-Ang O-Ang weak G15 O-Ang O-Ang O-Ang OH O-Ang O-Ang weak G16 O-Ang O-Ang OH O-Ang O-Ang O-Ang weak G17 O-Ang OH O-Ang O-Ang O-Ang O-Ang weak G18 OH O-Ang O-Ang O-Ang O-Ang O-Ang weak G19 O-Ang O-Ang O-Ang O-Ang O-Ang O-Ang none G20 O-Ang O-Ang OH OH OH O-Ang moderate G21 O-Ang O-Ang OH OH O-Ang OH moderate G22 O-Ang O-Ang OH O-Ang OH OH moderate G23 O-Ang O-Ang O-Ang OH OH OH moderate G24 O-Ang O-Ang OH OH OH OH moderate G25 O-Ang OH OH OH OH O-Ang moderate G26 OH O-Ang OH OH OH O-Ang moderate G27 OH OH O-Ang OH OH O-Ang moderate G28 OH OH OH O-Ang OH O-Ang moderate G29 O-Ang OH OH OH O-Ang OH moderate G30 OH O-Ang OH OH O-Ang OH moderate G31 OH OH O-Ang OH O-Ang OH moderate G32 OH OH OH O-Ang O-Ang OH moderate

Esterification of core compound E4A with (3,3-Dimethylartyloyl chloride) senecioyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A OH OH OH OH OH OH none B1 OH OH OH OH O-Sen OH moderate B2 OH OH OH OH OH O-Sen moderate B3 OH OH OH OH O-Sen O-Sen strong B4 O-Sen OH OH OH O-Sen O-Sen moderate B5 OH O-Sen OH OH O-Sen O-Sen moderate B6 OH OH O-Sen OH O-Sen O-Sen moderate B7 OH OH OH O-Sen O-Sen O-Sen moderate B8 O-Sen O-Sen OH OH O-Sen O-Sen weak B9 OH O-Sen O-Sen OH O-Sen O-Sen weak B10 OH OH O-Sen O-Sen O-Sen O-Sen weak B11 O-Sen OH O-Sen OH O-Sen O-Sen weak B12 OH O-Sen OH O-Sen O-Sen O-Sen weak B13 O-Sen OH OH O-Sen O-Sen O-Sen weak B14 OH O-Sen O-Sen OH O-Sen O-Sen weak B15 O-Sen O-Sen O-Sen OH O-Sen O-Sen weak B16 O-Sen O-Sen OH O-Sen O-Sen O-Sen weak B17 O-Sen OH O-Sen O-Sen O-Sen O-Sen weak B18 OH O-Sen O-Sen O-Sen O-Sen O-Sen weak B19 O-Sen O-Sen O-Sen O-Sen O-Sen O-Sen none B20 O-Sen O-Sen OH OH OH O-Sen moderate B21 O-Sen O-Sen OH OH O-Sen OH moderate B22 O-Sen O-Sen OH O-Sen OH OH moderate B23 O-Sen O-Sen O-Sen OH OH OH moderate B24 O-Sen O-Sen OH OH OH OH moderate B25 O-Sen OH OH OH OH O-Sen moderate B26 OH O-Sen OH OH OH O-Sen moderate B27 OH OH O-Sen OH OH O-Sen moderate B28 OH OH OH O-Sen OH O-Sen moderate B29 O-Sen OH OH OH O-Sen OH moderate B30 OH O-Sen OH OH O-Sen OH moderate B31 OH OH O-Sen OH O-Sen OH moderate B32 OH OH OH O-Sen O-Sen OH moderate Sen = senecioyl

Esterification of core compound E4A with 4-Pentenoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A OH OH OH OH OH OH none C1 OH OH OH OH O-Pen OH moderate C2 OH OH OH OH OH O-Pen moderate C3 OH OH OH OH O-Pen O-Pen strong C4 O-Pen OH OH OH O-Pen O-Pen moderate C5 OH O-Pen OH OH O-Pen O-Pen moderate C6 OH OH O-Pen OH O-Pen O-Pen moderate C7 OH OH OH O-Pen O-Pen O-Pen moderate C8 O-Pen O-Pen OH OH O-Pen O-Pen weak C9 OH O-Pen O-Pen OH O-Pen O-Pen weak C10 OH OH O-Pen O-Pen O-Pen O-Pen weak C11 O-Pen OH O-Pen OH O-Pen O-Pen weak C12 OH O-Pen OH O-Pen O-Pen O-Pen weak C13 O-Pen OH OH O-Pen O-Pen O-Pen weak C14 OH O-Pen O-Pen OH O-Pen O-Pen weak C15 O-Pen O-Pen O-Pen OH O-Pen O-Pen weak C16 O-Pen O-Pen OH O-Pen O-Pen O-Pen weak C17 O-Pen OH O-Pen O-Pen O-Pen O-Pen weak C18 OH O-Pen O-Pen O-Pen O-Pen O-Pen weak C19 O-Pen O-Pen O-Pen O-Pen O-Pen O-Pen none C20 O-Pen O-Pen OH OH OH O-Pen moderate C21 O-Pen O-Pen OH OH O-Pen OH moderate C22 O-Pen O-Pen OH O-Pen OH OH moderate C23 O-Pen O-Pen O-Pen OH OH OH moderate C24 O-Pen O-Pen OH OH OH OH moderate C25 O-Pen OH OH OH OH O-Pen moderate C26 OH O-Pen OH OH OH O-Pen moderate C27 OH OH O-Pen OH OH O-Pen moderate C28 OH OH OH O-Pen OH O-Pen moderate C29 O-Pen OH OH OH O-Pen OH moderate C30 OH O-Pen OH OH O-Pen OH moderate C31 OH OH O-Pen OH O-Pen OH moderate C32 OH OH OH O-Pen O-Pen OH moderate Pen = 4-Pentenoyl

Esterification of core compound E4A with Hexanoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4AF OH OH OH OH OH OH none D1 OH OH OH OH O-Hex OH moderate D2 OH OH OH OH OH O-Hex moderate D3 OH OH OH OH O-Hex O-Hex strong D4 O-Hex OH OH OH O-Hex O-Hex moderate D5 OH O-Hex OH OH O-Hex O-Hex moderate D6 OH OH O-Hex OH O-Hex O-Hex moderate D7 OH OH OH O-Hex O-Hex O-Hex moderate D8 O-Hex O-Hex OH OH O-Hex O-Hex weak D9 OH O-Hex O-Hex OH O-Hex O-Hex weak D10 OH OH O-Hex O-Hex O-Hex O-Hex weak D11 O-Hex OH O-Hex OH O-Hex O-Hex weak D12 OH O-Hex OH O-Hex O-Hex O-Hex weak D13 O-Hex OH OH O-Hex O-Hex O-Hex weak D14 OH O-Hex O-Hex OH O-Hex O-Hex weak D15 O-Hex O-Hex O-Hex OH O-Hex O-Hex weak D16 O-Hex O-Hex OH O-Hex O-Hex O-Hex weak D17 O-Hex OH O-Hex O-Hex O-Hex O-Hex weak D18 OH O-Hex O-Hex O-Hex O-Hex O-Hex weak D19 O-Hex O-Hex O-Hex O-Hex O-Hex O-Hex none D20 O-Hex O-Hex OH OH OH O-Hex moderate D21 O-Hex O-Hex OH OH O-Hex OH moderate D22 O-Hex O-Hex OH O-Hex OH OH moderate D23 O-Hex O-Hex O-Hex OH OH OH moderate D24 O-Hex O-Hex OH OH OH OH moderate D25 O-Hex OH OH OH OH O-Hex moderate D26 OH O-Hex OH OH OH O-Hex moderate D27 OH OH O-Hex OH OH O-Hex moderate D28 OH OH OH O-Hex OH O-Hex moderate D29 O-Hex OH OH OH O-Hex OH moderate D30 OH O-Hex OH OH O-Hex OH moderate D31 OH OH O-Hex OH O-Hex OH moderate D32 OH OH OH O-Hex O-Hex OH moderate Hex = Hexanoyl

Esterification of core compound E4A with 2-Ethylbutyryl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4AF OH OH OH OH OH OH none E1 OH OH OH OH O-Eth OH moderate E2 OH OH OH OH OH O-Eth moderate E3 OH OH OH OH O-Eth O-Eth strong E4 O-Eth OH OH OH O-Eth O-Eth moderate E5 OH O-Eth OH OH O-Eth O-Eth moderate E6 OH OH O-Eth OH O-Eth O-Eth moderate E7 OH OH OH O-Eth O-Eth O-Eth moderate E8 O-Eth O-Eth OH OH O-Eth O-Eth weak E9 OH O-Eth O-Eth OH O-Eth O-Eth weak E10 OH OH O-Eth O-Eth O-Eth O-Eth weak E11 O-Eth OH O-Eth OH O-Eth O-Eth weak E12 OH O-Eth OH O-Eth O-Eth O-Eth weak E13 O-Eth OH OH O-Eth O-Eth O-Eth weak E14 OH O-Eth O-Eth OH O-Eth O-Eth weak E15 O-Eth O-Eth O-Eth OH O-Eth O-Eth weak E16 O-Eth O-Eth OH O-Eth O-Eth O-Eth weak E17 O-Eth OH O-Eth O-Eth O-Eth O-Eth weak E18 OH O-Eth O-Eth O-Eth O-Eth O-Eth weak E19 O-Eth O-Eth O-Eth O-Eth O-Eth O-Eth none E20 O-Eth O-Eth OH OH OH O-Eth moderate E21 O-Eth O-Eth OH OH O-Eth OH moderate E22 O-Eth O-Eth OH O-Eth OH OH moderate E23 O-Eth O-Eth O-Eth OH OH OH moderate E24 O-Eth O-Eth OH OH OH OH moderate E25 O-Eth OH OH OH OH O-Eth moderate E26 OH O-Eth OH OH OH O-Eth moderate E27 OH OH O-Eth OH OH O-Eth moderate E28 OH OH OH O-Eth OH O-Eth moderate E29 O-Eth OH OH OH O-Eth OH moderate E30 OH O-Eth OH OH O-Eth OH moderate E31 OH OH O-Eth OH O-Eth OH moderate E32 OH OH OH O-Eth O-Eth OH moderate Eth = 2-Ethylbutyryl

Esterification of core compound E4A with Acetyl chloride (H) and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A OH OH OH OH OH OH none H1 OH OH OH OH O-Acy OH moderate H2 OH OH OH OH OH O-Acy moderate H3 OH OH OH OH O-Acy O-Acy strong H4 O-Acy OH OH OH O-Acy O-Acy moderate H5 OH O-Acy OH OH O-Acy O-Acy moderate H6 OH OH O-Acy OH O-Acy O-Acy moderate H7 OH OH OH O-Acy O-Acy O-Acy moderate H8 O-Acy O-Acy OH OH O-Acy O-Acy weak H9 OH O-Acy O-Acy OH O-Acy O-Acy weak H10 OH OH O-Acy O-Acy O-Acy O-Acy weak H11 O-Acy OH O-Acy OH O-Acy O-Acy weak H12 OH O-Acy OH O-Acy O-Acy O-Acy weak H13 O-Acy OH OH O-Acy O-Acy O-Acy weak H14 OH O-Acy O-Acy OH O-Acy O-Acy weak H15 O-Acy O-Acy O-Acy OH O-Acy O-Acy weak H16 O-Acy O-Acy OH O-Acy O-Acy O-Acy weak H17 O-Acy OH O-Acy O-Acy O-Acy O-Acy weak H18 OH O-Acy O-Acy O-Acy O-Acy O-Acy weak H19 O-Acy O-Acy O-Acy O-Acy O-Acy O-Acy none H20 O-Acy O-Acy OH OH OH O-Acy moderate H21 O-Acy O-Acy OH OH O-Acy OH moderate H22 O-Acy O-Acy OH O-Acy OH OH moderate H23 O-Acy O-Acy O-Acy OH OH OH moderate H24 O-Acy O-Acy OH OH OH OH moderate H25 O-Acy OH OH OH OH O-Acy moderate H26 OH O-Acy OH OH OH O-Acy moderate H27 OH OH O-Acy OH OH O-Acy moderate H28 OH OH OH O-Acy OH O-Acy moderate H29 O-Acy OH OH OH O-Acy OH moderate H30 OH O-Acy OH OH O-Acy OH moderate H31 OH OH O-Acy OH O-Acy OH moderate H32 OH OH OH O-Acy O-Acy OH moderate Acy = Acetyl

Esterification of core compound E4A with Crotonoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A OH OH OH OH OH OH none I1 OH OH OH OH O-Cro OH moderate I2 OH OH OH OH OH O-Cro moderate I3 OH OH OH OH O-Cro O-Cro strong I4 O-Cro OH OH OH O-Cro O-Cro moderate I5 OH O-Cro OH OH O-Cro O-Cro moderate I6 OH OH O-Cro OH O-Cro O-Cro moderate I7 OH OH OH O-Cro O-Cro O-Cro moderate I8 O-Cro O-Cro OH OH O-Cro O-Cro weak I9 OH O-Cro O-Cro OH O-Cro O-Cro weak I10 OH OH O-Cro O-Cro O-Cro O-Cro weak I11 O-Cro OH O-Cro OH O-Cro O-Cro weak I12 OH O-Cro OH O-Cro O-Cro O-Cro weak I13 O-Cro OH OH O-Cro O-Cro O-Cro weak I14 OH O-Cro O-Cro OH O-Cro O-Cro weak I15 O-Cro O-Cro O-Cro OH O-Cro O-Cro weak I16 O-Cro O-Cro OH O-Cro O-Cro O-Cro weak I17 O-Cro OH O-Cro O-Cro O-Cro O-Cro weak I18 OH O-Cro O-Cro O-Cro O-Cro O-Cro weak I19 O-Cro O-Cro O-Cro O-Cro O-Cro O-Cro none I20 O-Cro O-Cro OH OH OH O-Cro moderate I21 O-Cro O-Cro OH OH O-Cro OH moderate I22 O-Cro O-Cro OH O-Cro OH OH moderate I23 O-Cro O-Cro O-Cro OH OH OH moderate I24 O-Cro O-Cro OH OH OH OH moderate I25 O-Cro OH OH OH OH O-Cro moderate I26 OH O-Cro OH OH OH O-Cro moderate I27 OH OH O-Cro OH OH O-Cro moderate Cro = Crotonoyl

Esterification of core compound E4A with Cinnamoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A OH OH OH OH OH OH none J1 OH OH OH OH O-Cin OH moderate J2 OH OH OH OH OH O-Cin moderate J3 OH OH OH OH O-Cin O-Cin strong J4 O-Cin OH OH OH O-Cin O-Cin moderate J5 OH O-Cin OH OH O-Cin O-Cin moderate J6 OH OH O-Cin OH O-Cin O-Cin moderate J7 OH OH OH O-Cin O-Cin O-Cin moderate J8 O-Cin O-Cin OH OH O-Cin O-Cin weak J9 OH O-Cin O-Cin OH O-Cin O-Cin weak J10 OH OH O-Cin O-Cin O-Cin O-Cin weak J11 O-Cin OH O-Cin OH O-Cin O-Cin weak J12 OH O-Cin OH O-Cin O-Cin O-Cin weak J13 O-Cin OH OH O-Cin O-Cin O-Cin weak J14 OH O-Cin O-Cin OH O-Cin O-Cin weak J15 O-Cin O-Cin O-Cin OH O-Cin O-Cin weak J16 O-Cin O-Cin OH O-Cin O-Cin O-Cin weak J17 O-Cin OH O-Cin O-Cin O-Cin O-Cin weak J18 OH O-Cin O-Cin O-Cin O-Cin O-Cin weak J19 O-Cin O-Cin O-Cin O-Cin O-Cin O-Cin none J20 O-Cin O-Cin OH OH OH O-Cin moderate J21 O-Cin O-Cin OH OH O-Cin OH moderate J22 O-Cin O-Cin OH O-Cin OH OH moderate J23 O-Cin O-Cin O-Cin OH OH OH moderate J24 O-Cin O-Cin OH OH OH OH moderate J25 O-Cin OH OH OH OH O-Cin moderate J26 OH O-Cin OH OH OH O-Cin moderate J27 OH OH O-Cin OH OH O-Cin moderate J28 OH OH OH O-Cin OH O-Cin moderate J29 O-Cin OH OH OH O-Cin OH moderate J30 OH O-Cin OH OH O-Cin OH moderate J31 OH OH O-Cin OH O-Cin OH moderate J32 OH OH OH O-Cin O-Cin OH moderate Cin = Cinnamoyl

Esterification of core compound E4A with benzoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A OH OH OH OH OH OH none K1 OH OH OH OH O-Ben OH moderate K2 OH OH OH OH OH O-Ben moderate K3 OH OH OH OH O-Ben O-Ben strong K4 O-Ben OH OH OH O-Ben O-Ben moderate K5 OH O-Ben OH OH O-Ben O-Ben moderate K6 OH OH O-Ben OH O-Ben O-Ben moderate K7 OH OH OH O-Ben O-Ben O-Ben moderate K8 O-Ben O-Ben OH OH O-Ben O-Ben weak K9 OH O-Ben O-Ben OH O-Ben O-Ben weak K10 OH OH O-Ben O-Ben O-Ben O-Ben weak K11 O-Ben OH O-Ben OH O-Ben O-Ben weak K12 OH O-Ben OH O-Ben O-Ben O-Ben weak K13 O-Ben OH OH O-Ben O-Ben O-Ben weak K14 OH O-Ben O-Ben OH O-Ben O-Ben weak K15 O-Ben O-Ben O-Ben OH O-Ben O-Ben weak K16 O-Ben O-Ben OH O-Ben O-Ben O-Ben weak K17 O-Ben OH O-Ben O-Ben O-Ben O-Ben weak K18 OH O-Ben O-Ben O-Ben O-Ben O-Ben weak K19 O-Ben O-Ben O-Ben O-Ben O-Ben O-Ben none K20 O-Ben O-Ben OH OH OH O-Ben moderate K21 O-Ben O-Ben OH OH O-Ben OH moderate K22 O-Ben O-Ben OH O-Ben OH OH moderate K23 O-Ben O-Ben O-Ben OH OH OH moderate K24 O-Ben O-Ben OH OH OH OH moderate K25 O-Ben OH OH OH OH O-Ben moderate K26 OH O-Ben OH OH OH O-Ben moderate K27 OH OH O-Ben OH OH O-Ben moderate K28 OH OH OH O-Ben OH O-Ben moderate K29 O-Ben OH OH OH O-Ben OH moderate K30 OH O-Ben OH OH O-Ben OH moderate K31 OH OH O-Ben OH O-Ben OH moderate K32 OH OH OH O-Ben O-Ben OH moderate Ben = benzoyl

Esterification of E4A-Tig-N with senecioyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Sen-1 OH OH OH OH O-Tig O-Sen strong Tig-Sen-2 O-Sen OH OH OH O-Tig O-Sen moderate Tig-Sen-3 OH O-Sen OH OH O-Tig O-Sen moderate Tig-Sen-4 OH OH O-Sen OH O-Tig O-Sen moderate Tig-Sen-5 O-Sen OH OH OH O-Tig OH moderate Tig-Sen-6 OH O-Sen OH OH O-Tig OH moderate

Esterification of E4A-Tig-N with Crotonoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Cro-1 OH OH OH OH O-Tig O-Cro strong Tig-Cro-2 O-Cro OH OH OH O-Tig O-Cro moderate Tig-Cro-3 OH O-Cro OH OH O-Tig O-Cro moderate Tig-Cro-4 OH OH O-Cro OH O-Tig O-Cro moderate Tig-Cro-5 O-Cro OH OH OH O-Tig OH moderate Tig-Cro-6 OH O-Cro OH OH O-Tig OH moderate

Esterification of E4A-Tig-N with Acetyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Acy-1 OH OH OH OH O-Tig O-Acy strong Tig-Acy-2 O-Acy OH OH OH O-Tig O-Acy moderate Tig-Acy-3 OH O-Acy OH OH O-Tig O-Acy moderate Tig-Acy-4 OH OH O-Acy OH O-Tig O-Acy moderate Tig-Acy-5 O-Acy OH OH OH O-Tig OH moderate Tig-Acy-6 OH O-Acy OH OH O-Tig OH moderate

Esterification of E4A-Tig-N with 4-Pentenoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Pen-1 OH OH OH OH O-Tig O-Pen strong Tig-Pen-2 O-Pen OH OH OH O-Tig O-Pen moderate Tig-Pen-3 OH O-Pen OH OH O-Tig O-Pen moderate Tig-Pen-4 OH OH O-Pen OH O-Tig O-Pen moderate Tig-Pen-5 O-Pen OH OH OH O-Tig OH moderate Tig-Pen-6 OH O-Pen OH OH O-Tig OH moderate

Esterification of E4A-Tig-N with Hexanoly chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Hex-1 OH OH OH OH O-Tig O-Hex strong Tig-Hex-2 O-Hex OH OH OH O-Tig O-Hex moderate Tig-Hex-3 OH O-Hex OH OH O-Tig O-Hex moderate Tig-Hex-4 OH OH O-Hex OH O-Tig O-Hex moderate Tig-Hex-5 O-Hex OH OH OH O-Tig OH moderate Tig-Hex-6 OH O-Hex OH OH O-Tig OH moderate

Esterification of E4A-Tig-N with Cinnamoyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Cin-1 OH OH OH OH O-Tig O-Cin strong Tig-Cin-2 O-Cin OH OH OH O-Tig O-Cin moderate Tig-Cin-3 OH O-Cin OH OH O-Tig O-Cin moderate Tig-Cin-4 OH OH O-Cin OH O-Tig O-Cin moderate Tig-Cin-5 O-Cin OH OH OH O-Tig OH moderate Tig-Cin-6 OH O-Cin OH OH O-Tig OH moderate

Esterification of E4A-Tig-N with Angeloyl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Ang-1 OH OH OH OH O-Tig O-Ang strong Tig-Ang-2 O-Ang OH OH OH O-Tig O-Ang moderate Tig-Ang-3 OH O-Ang OH OH O-Tig O-Ang moderate Tig-Ang-4 OH OH O-Ang OH O-Tig O-Ang moderate Tig-Ang-5 O-Ang OH OH OH O-Tig OH moderate Tig-Ang-6 OH O-Ang OH OH O-Tig OH moderate

Esterification of E4A-Tig-N with 2-Ethylbutyryl chloride and isolation of the compounds with HPLC give the following compounds:

Cytotoxicity R1 R2 R5 R8 R17 R18 activity E4A-Tig-N OH OH OH OH O-Tig OH moderate Tig-Eth-1 OH OH OH OH O-Tig O-Eth strong Tig-Eth-2 O-Eth OH OH OH O-Tig O-Eth moderate Tig-Eth-3 OH O-Eth OH OH O-Tig O-Eth moderate Tig-Eth-4 OH OH O-Eth OH O-Tig O-Eth moderate Tig-Eth-5 O-Eth OH OH OH O-Tig OH moderate Tig-Eth-6 OH O-Eth OH OH O-Tig OH moderate

Esterification of compound (A), (B), (C), (D), (E), (F), (G), (H) with acyl chloride including Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride or Ethylbutyryl chloride The compounds vary in composition when the time or temperature of the reaction is changed. The peaks, fractions and compounds are selected according to the activities of times studies and the changes of peaks. The compounds having strong to weak activities are selected and isolated. The anti cancer activities are the MTT studies of bone (U2OS), lung (H460), bladder(HTB-9), ovary (ES2), colon (HCT116), pancreas (Capan), ovary(OVCAR3), prostate (DU145), skin (SK-Mel-5), mouth (KB), kidney (A498), breast (MCF-7), liver (HepG2), brain (T98G), luekemia (K562), cervix (HeLa). The active esterification products are purified with HPLC. The reaction product of mixtures and individual compounds are tested with MTT Cytotoxic Assay. Details of method are in Experiment 3 of the present application. A second esterification of compound can be selected from the above experiment results to produce new active compounds. A partial esterification compound is selected from the above experiments to perform a second or repeated with a third esterification with different acyl chloride in order to produce new active compounds with the experiments in the present application.

A method is 1) Dissolving core compound or triterpenes core, hydroxylated triterpenes core in pyridine; 2) Adding acyl chloride; 3, The mixture is stirred for length of time including 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at different temperature; 4) At the end of reaction, aqueous solution of acid or weak base, or water is added to the reaction mixture; 5) The solution is then extracted of ethyl acetate and lyophilization; 6) Dissolving the reaction product in acetonitrile with Trifluoroacetic acid or DMSO; 7) Testing the reaction product of mixtures and individual fractions with MTT cytotoxic assay; 8) Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific reaction time; 10) Purifiing the active esterification products with HPLC; 11) Collecting the products; 12) Testing the products; wherein the core compound is terpene, isoprene, or triterpene core or hydroxylated triterpenes core; wherein the core compound was dissolved in pyridine; wherein the acyl chloride including Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride and Ethylbutyryl chloride; wherein the reaction time for the mixture is stirred for 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days; wherein the temperature is 0C, 25C, 50 or 75C temperature; wherein the acid including HCl or the base including NaHCO3 is added to the reaction mixture; wherein the solution is then extracted 3 times with ethyl acetate and lyophilization; wherein the reaction product is dissolved in 80% acetonitrile—0.005% Trifluoroacetic acid or DMSO; wherein selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a reaction time of 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days. In an embodiment, the reaction time may be ove 3 days. In an embodiment, the experiment may be performed under 0C. In an embodiment, the experiment may be performed over 75C.

The anti cancer activities of Tig-R compound: IC50 of bone (U2OS) is 4.5 ug/ml, lung (H460) is 4.8 ug/ml, bladder(HTB-9) is 2.5 ug/ml, ovary (ES2) is 2.8 ug/ml, colon (HCT116) is 5.2 ug/ml, pancreas (Capan) 2.4 ug/ml, ovary(OVCAR3) is 5.8, prostate (DU145) is 3.6 ug/ml, skin (SK-Mel-5) is 5.1 ug/ml, mouth (KB) is 3 ug/ml, kidney (A498) is 3.5 ug/ml, breast (MCF-7) is 4.5 ug/ml, liver (HepG2) is 6 ug/ml, brain (T98G) is 8 ug/ml), leukemia (K562) is 2 ug/ml, cervix (HeLa) is 5 ug/ml.

The anti cancer activities of Tig-V compound: IC50 of bone (U2OS) is 7 ug/ml, lung (H460) is 6.8 ug/ml, bladder(HTB-9) is 4 ug/ml, ovary (ES2) is 2 ug/ml, colon (HCT116) is 8 ug/ml, pancreas (Capan) 5 ug/ml, ovary(OVCAR3) is 9, prostate (DU145) is 4 ug/ml, skin (SK-Mel-5) is 6 ug/ml, mouth (KB) is 4.5 ug/ml, kidney (A498) is 4.8 ug/ml, breast (MCF-7) is 9 ug/ml, liver (HepG2) is 12 ug/ml, brain (T98G) is 14 ug/ml), leukemia (K562) is 4 ug/ml, cervix (HeLa) is 7 ug/ml.

The anti cancer activities of Tig-N compound: IC50 of bone (U2OS) is 15 ug/ml, lung (H460) is 13 ug/ml, bladder(HTB-9) is 7.5 ug/ml, ovary (ES2) is 9 ug/ml, colon (HCT116) is 15 ug/ml, pancreas (Capan) 8 ug/ml, ovary(OVCAR3) is 18, prostate (DU145) is 4.8 ug/ml, skin (SK-Mel-5) is 15 ug/ml, mouth (KB) is 9 ug/ml, kidney (A498) is 11 ug/ml, breast (MCF-7) is 13 ug/ml, liver (HepG2) is 18 ug/ml, brain (T98G) is 19 ug/ml), leukemia (K562) is 6 ug/ml, cervix (HeLa) is 15 ug/ml.

The anti cancer activities of Tig-Q compound: IC50 of bone (U2OS) is 20 ug/ml, lung (H460) is 18 ug/ml, bladder(HTB-9) is 10 ug/ml, ovary (ES2) is 12 ug/ml, colon (HCT116) is 22 ug/ml, pancreas (Capan) 9 ug/ml, ovary(OVCAR3) is 23, prostate (DU145) is 15 ug/ml, skin (SK-Mel-5) is 20 ug/ml, mouth (KB) is 12 ug/ml, kidney (A498) is 13 ug/ml, breast (MCF-7) is 18 ug/ml, liver (HepG2) is 24 ug/ml, brain (T98G) is 29 ug/ml), leukemia (K562) is 6 ug/ml, cervix (HeLa) is 20 ug/ml.

The anti cancer activities of Tig-T compound: IC50 of bone (U2OS) is 20 ug/ml, lung (H460) is 21 ug/ml, bladder(HTB-9) is 12 ug/ml, ovary (ES2) is 14 ug/ml, colon (HCT116) is 23 ug/ml, pancreas (Capan) 10 ug/ml, ovary(OVCAR3) is 25, prostate (DU145) is 16 ug/ml, skin (SK-Mel-5) is 22 ug/ml, mouth (KB) is 13 ug/ml, kidney (A498) is 15 ug/ml, breast (MCF-7) is 20 ug/ml, liver (HepG2) is 26 ug/ml, brain (T98G) is 26 ug/ml), leukemia (K562) is 9 ug/ml, cervix (HeLa) is 18 ug/ml.

The anti cancer activities of Tig-S compound: IC50 of bone (U2OS) is 5.2 ug/ml, lung (H460) is 5.6 ug/ml, bladder(HTB-9) is 3.5 ug/ml, ovary (ES2) is 4.2 ug/ml, colon (HCT116) is 6.6 ug/ml, pancreas (Capan) 2.9 ug/ml, ovary(OVCAR3) is 6.5, prostate (DU145) is 4.3 ug/ml, skin (SK-Mel-5) is 5.8 ug/ml, mouth (KB) is 4 ug/ml, kidney (A498) is 4.8 ug/ml, breast (MCF-7) is 6.3 ug/ml, liver (HepG2) is 8.5 ug/ml, brain (T98G) is 9 ug/ml), leukemia (K562) is 4.3 ug/ml, cervix (HeLa) is 7 ug/ml.

The anti cancer activities of Tig-U compound: IC50 of bone (U2OS) is 23 ug/ml, lung (H460) is 19 ug/ml, bladder(HTB-9) is 15 ug/ml, ovary (ES2) is 17 ug/ml, colon (HCT116) is 26 ug/ml, pancreas (Capan) 9 ug/ml, ovary(OVCAR3) is 27, prostate (DU145) is 15 ug/ml, skin (SK-Mel-5) is 24 ug/ml, mouth (KB) is 16 ug/ml, kidney (A498) is 18 ug/ml, breast (MCF-7) is 25 ug/ml, liver (HepG2) is 23 ug/ml, brain (T98G) is 22 ug/ml), leukemia (K562) is 10 ug/ml, cervix (HeLa) is 17 ug/ml.

This invention provides compounds, methods, or uses of a compound for the manufacture of a medicament, or uses of a compound for medicament selected from formula (2A), for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, using compounds selected from the following:

R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14, R15 are independently selected from the group of hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl,alkane, alkene and sugar moiety or derivatives thereof; wherein the structure (2A) comprises at least 2 groups selected from O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; or wherein R1 and R2 are selected from O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; In an embodiment, wherein the R1 and R2 are attached OH. In an embodiment, wherein R4, R10 are attached a CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, or CH2O-Ethylbutyryl. In an embodiment, wherein the R3 and R8 is hydrogen or hydroxyl, In an embodiment, wherein the R9, R11, R12, R13, R14, R15 are independently attached with a methyl. In an embodiment, wherein R4 represents CH3, CHO, CH₂R6 or CORE, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; In an embodiment, wherein R3 is H or OH; In an embodiment, wherein R8 is H or OH; In an embodiment, wherein R16 is H, CH3, OH, or R4 and R16 may together form —CH2—X—, CH(OH)—X— or C(═O)—X—, wherein the —X— may be O or NH or S; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent. In an embodiment, wherein R10 represents CH3, CHO, or CH₂R6, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof;

In an embodiment, wherein R5 is a hydrogen, hydroxyl, heterocyclic or O-sugar moiety(ies), wherein the sugar moiety(ies) is/are selected from a group consisting of glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, alduronic acid, glucuronic acid, galacturonic acid, and derivatives or combinations thereof; wherein R9, R10, R11, R12, R13, R14, R15 are independently attached a group selecting from CH₃, CH₂OH, CHO, COOH, COO-alkyl, COO-aryl, COO-heterocyclic, COO-heteroaryl, CH₂Oaryl, CH₂O— heterocyclic, CH₂O— heteroaryl, alkyls group, hydroxyl, acetyl group; wherein R4 and R16 form a divalent radical of formula CH2O, CH(OR7)O, or COOR7, wherein R7 is hydrogen, alkyl, angeloyl, tigloyl, senecioyl, dibenzoyl, benzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and derivatives thereof; wherein at least two of R1, R2 and R6 are attached a group selected from O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, and derivatives thereof; or at least one of R1, R2, and R4 is a sugar moiety having at least two groups selected from a group consisting of angeloyl, acetyl, tigloyl, senecioyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, benzoyl, dibenzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, aryl, acyl, heterocylic, heteroraryl, and their derivatives thereof; or wherein R4 represents CH₂R6, wherein R6 is selected from hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof; wherein R5 is/are the sugar moiety(ies) selected from the following sugars and alduronic acids: glucose, galactose, rhamnose, arabinose, xylose, fucose, allose, altrose, gulose, idose, lyxose, mannose, psicose, ribose, sorbose, tagatose, talose, fructose, glucuronic acid, galacturonic acid; or their derivatives thereof, In an embodiment, wherein R5 is a hydroxyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl and derivatives thereof. In an embodiment, R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14 or R15 comprise of one or more sugar moieties. In an embodiment, R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14 or R15 comprise of one or more acids. In an embodiment, at least 1, or 2, or 3, or 4 of R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14 and R15 is hydroxyl. In an embodiment, at least 2, or 3, or 4, or 5, or 6, or 7 of R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14 and R15 are independently attached a group selected from the group of O-acetyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, alkane, alkene and derivatives thereof, wherein the group is attached to the triterpene directly or by connecting moiety(ies); In an embodiment, at least 1 or 2, or 3, or 4, or 5, or 6, or 7 of R1, R2, R3, R4, R5, R8 and R10 are independently attached a group selected from the group of O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH3, CH2OH, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, D-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, and derivatives thereof, wherein the group is attached to the triterpene directly or by connecting moiety(ies). In an embodiment, the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells comprise breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell. In an embodiment, the compound is selected from the structure:

R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14, R15 are independently selected from the group of CH3, CH2OH, hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl,alkane, alkene and sugar moiety or derivatives thereof; or

wherein any 1 or 2 or 3 or 4 of R1, R2, R3, R4, R5, R8 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl; R9, R11, R12, R13, R14, R15 are independently attached a CH3; or wherein R10 is attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl; or wherein R4 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl; wherein R3 is OH or H or absent; wherein R1, R2, R3, R5, R8 are OH or H or absent; wherein R9, R11, R12, R13, R14, and R15 are CH3; or wherein R1, R2, R5, R8 represent OH; R3 represents OH, H or absent; R4, R10 represent CH2Oangeloyl; R9, R11, R12, R13, R14, R15 represent CH3; or wherein R1, R2, R5, R8 represent OH or O-tigloyl; R3 represents OH, H, or absent; R4, R10 represent CH2O tigloyl; R9, R11, R12, R13, R14, R15 represent CH3; wherein the group attaching to the core compound selected from acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, O-3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl and alkenylcarbonyl are interchangeable. They can be the same group or in combination thereof. Substitution, deletion and/or addition of any group in the above-described compounds by other group(s) will be apparent to one of ordinary skill in the art based on the teachings of this application. In a further embodiment, the substitution, deletion and/or addition of the group(s) in the compound of the invention does not substantially affect the biological function of the compound.

In an embodiment, the compound is selected from the structures:

A composition comprising an effective amount of compound selected from the above formula or a salt, ester, metabolite or derivative thereof can be used as a medicament for blocking the invasion, migration, metastasis of cancer cells, inhibiting tumor or cancer cell growth and for treating cancer, wherein the cancers comprise breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer.

This invention provides a composition comprising the compounds provided in the invention for treating cancers; for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular diseasea; inhibiting NF-Kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for AntiMS, antianeurysm, antiasthmatic, anti-oedematous, anti-inflammatory, antibradykinic, anticapillarihemorrhagic, anticephalagic, anticervicobrachialgic, antieclamptic, antiedemic, antiencaphalitic, antiepiglottitic, antiexudative, antiflu, antifracture, antigingivitic, antihematomic, antiherpetic, antihistaminic, antihydrathritic, antimeningitic, antioxidant, antiperiodontic, antiphlebitic, antipleuritic, antiraucedo, antirhinitic, antitonsilitic, antiulcer, antivaricose, antivertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cancer cells, antiparasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z, and manufacturing an adjuvant composition and venotonic treatment.

Alkenyl means unsaturated linear or branched structures and combinations thereof, having formula R2C═CR2, one or more double bonds therein. Examples of alkenyl groups include vinyl, propenyl, isopropenyl, butenyl, s- and t-butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, and hexadienyl.

An aryl is a functional group of organic molecule derived from an aromatic compound such as benzene, a 6-14 membered carbocyclic aromatic ring system comprising 1-3 benzene rings. If two or more aromatic rings are present, then the rings are fused together, so that adjacent rings share a common bond. Examples include phenyl and naphthyl. The aryl group may be substituted with one or more substitutes independently selected from halogen, alkyl or alkoxy.

Acyl is a functional group which can be obtained from an organic acid by the removal of the carboxyl. Acyl groups can be written using the general formula —COR, where there is a double bond between the carbon and oxygen. The names of acyl groups typically end in -yl, such as formyl, acetyl, propionyl, butyryl and benzoyl. Benzoyl is one of the acyls, C₆H₅COR, obtained from benzoic acid by the removal of the carboxyl.

A heterocyclic compound is a compound containing a heterocyclic ring which refers to a non-aromatic ring having 1-4 heteroatoms, said ring being isolated or fused to a second ring selected from 3- to 7-membered alicyclic ring containing 0-4 heteroatoms, aryl and heteroaryl, wherein heterocyclic compounds include pyrrolidinyl, pipyrazinyl, morpholinyl, trahydrofuranyl, imidazolinyl, thiomorpholinyl, and the like.

Heterocyclyl groups are derived from heteroarenes by removal of a hydrogen atom from any ring atom.

Alkanoyl is the general name for an organic functional group RCO—, where R represents hydrogen or an alkyl group. Examples of alkanoyls are acetyl, propionoyl, butyryl, isobutyryl, pentanoyl and hexanoyl.

Alkenoyl is an alkenylcarbonyl in which the alkenyl is defined above. Examples are pentenoyl(tigloyl) and hexenoyl(angeloyl).

Alkyl is a radical containing only carbon and hydrogen atoms arranged in a chain, branched, cyclic or bicyclic structure or their combinations, having 1-18 carbon atoms. Examples include but are not limited to methyl, ethyl, propyl isopropyl, butyl, s- and t-butyl, pentyl, hexyl, heptyl, octyl, nonyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

Benzoyl alkyl substituted alkanoyl refers to straight or branched alkanoyl substituted with at least one benzoyl and at least one alkyl, wherein the benzoyl is attached to a straight or branched alkyl. An example of a benzoyl alkyl substituted alkanoyl is benzoyl methyl isobutanoyl.

A sugar moiety is a segment of molecule comprising one or more sugars or derivatives thereof or alduronic acid thereof.

Isobutyryl is a synonym of 2-Methylpropanoyl (Y)Y3, Y and Y3 represent the same compound. YM and (ACH-Y) represent the same compound.

Connecting moiety is a substructure or a group of atoms which connect the functional group to a core compound. Example: angeloyl group is connected by a sugar moiety to a triterpene core.

The building blocks used in the invention including triterpenes, hydroxylated triterpenes, acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, O-3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, alkenylcarbonyl, acetyl chloride, angeloyl chloride, tigloyl chloride, senecioyl chloride, Crotonoyl chloride, O-3,3-Dimethylartyloyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride, Ethylbutyryl chloride.

In the presented experiments, concentrations of drug that inhibit 15% cell-growth or less (i.e. 85% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 10% cell-growth or less (i.e. 90% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 5% cell-growth or less (i.e. 95% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 20% cell-growth or less (i.e. 80% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 25% cell-growth or less (i.e. 75% of control or above) as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 30% cell-growth or less as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations. In an embodiment, the concentrations of drug that inhibit 45% cell-growth or less as compared to the no-drug control (DMSO) are considered non-cytotoxic concentrations.

The triterpene compound or compounds selected from this invention can be administered to a subject in need thereof, treating the subject, wherein including preventing cancer, or providing an adjuvant effect to the subject, or inhibiting the initation or promotion of cancer, or killing the cancer/tumor cells, or inhibiting cancer cell invasion. In an embodiment the compounds inhibit the activation of nuclear factor-kB, wherein inhibiting the localization or wherein binding the DNA. In an embodiment the compounds induce apoptosis in cancer cells.

Table 1 to 12, Effect of Y and YM on gene expression (Table of 1 to 12 PCT/US2008/002086, 1188-ALA-PCT, filed Feb. 15, 2008 are incorporated herein by reference) Table 13 to 19, Effect of Y and YM on gene expression (Table of 13 to 19 PCT/US2009/034115, 1188-D-PCT, filed Feb. 15, 2008 are incorporated herein by reference)

Determination of Gene Expression by Real-Time PCR Method (Brilliant QPCR, Agilent Technologies):

The real-time polymerase chain reactions further confirm the results obtained from microarray analysis. The Real-time PCR results (shown below) confirmed that Compound Y3 and YM increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z, wherein the results in Table 19-21 disclosed in PCT/US09/34115, filed Feb. 13, 2009 are incorporated herein by reference.

The saponins are partially hydrolyzed into a mixture of products which can be separated by HPLC. Specific partial hydrolysis of saponins can also be achieved with enzymes. The glycosidases catalyze the hydrolysis of the glycosidic linkage. Galactosidase is an enzyme which catalyzes the hydrolysis of galactosides. Glucosidase is an enzyme which breaks glucose from saponin. Other enzyme examples are xylanases, lactase, amylase, chitinase, sucrase, maltase, and neuraminidase.

The sugar moiety of the triterpenoid saponin (example Xanifolia Y) can be removed by acid hydrolysis. The synthetic compound of ACH-Y is obtained. ACH-Y is a triterpene with acyl groups but no sugar moiety. The acyl group of the saponin (example Xanifolia Y) can be removed by alkaline hydrolysis. The synthetic compound AKOH-Y can be obtained. AKOH-Y is a pentacyclic triterpene with sugar moieties. A pentacyclic triterpene can be obtained by acid and alkaline hydroysis of saponins from natural sources. A pentacyclic triterpene can be obtained by synthetic methods (Reference: Surendra et al., Rapid and Enantioselective Synthetic Approches to Germanicol and Other Pentacyclic Triterpenes, Journal of the American Chemical Society, 2008, 130(27), 8865-8869). Pentacyclic triterpenes with sugar moieties can also be obtained by synthesis (Reference: Ple et al., Synthesis of L-arabinopyranose containing hederagenin saponins, Tetrahedron 61 (2005) 4347-4362). Acylation is the process of adding an acyl group to a compound. The Friedel-Crafts reaction is an example of this process. An active compound can be obtained by acylating a pentacyclic triterpenes, or hydroxylated triterpenes. In an embodiment, acylating C24, C28, C21 and C22 of a pentacyclic triterpenes, or hydroxylated triterpenes produce compounds for inhibiting cancer growth, cancer invasion, cell invasion, cancer cell invasion, cell attachment adhesion, or cell circulation. In an embodiment, the acyl group(s) may be at C3. In an embodiment, a sugar moiety is at C21, 22, or 28, wherein the sugar moiety is attached with 2 acyl groups. In an embodiment, acylating the compounds of (A), (B), (C), (D), (F), (G), (H), produce the compounds for inhibiting cancer invasion, cells invasion or cancer cell invasion; cancer metastasis; or cancer growth The building blocks in the present application are used to synthesise active saponins.

Acylating the compound (G) with angeloyl or tigloyl group gives the following compounds

wherein R1, R2, R5, R8 represent OH or O-angeloyl; R3 represents OH, H or O-angeloyl; R4, R10 represent CH3, CH2OH or CH2Oangeloyl; R3 represents OH, H or O-angeloyl; R9, R11, R12, R13, R14, R15 represent CH3; or wherein R1, R2, R5, R8 represent OH or O-tigloyl; R3 represents OH, H or O-tigloyl; R4, R10 represent CH3, CH2OH or CH2O tigloyl; R9, R11, R12, R13, R14, R15 represent CH3; wherein the compounds inhibit cancer growth, cancer invasion, cells invasion or cancer cell invasion.

Acylating the compound (G) with angeloyl, tigloyl, senecioyl, acetyl, Crotonoyl, 3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted O-alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl, CH2O-alkenylcarbonyl, alkane, alkene give the compound (K) wherein R1, R2, R5, R8 represent OH, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; R4, R10 represent CH3, CH2OH, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-Crotonoyl, CH2O-3,3-Dimethylartyloyl, CH2O-Cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl,alkane, alkene; R3 is absent of represents OH, H, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-Crotonoyl, O-3,3-Dimethylartyloyl, O-Cinnamoyl, O-Pentenoyl, O-Hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; wherein R9, R11, R12, R13, R14, R15 represent CH3; wherein the compounds inhibit cancer growth, cancer invasion, cells invasion or cancer cell invasion; wherein the compound for use as mediator or inhibitor of adhesion protein or angiopoietin; wherein the compounds use as mediator modulating the secretion, expression, or synthesis of adhesion protein comprises reducing the fibronectin for inhibiting cell attachment, cell adhesion or cell circulation; wherein the adhesion proteins comprise fibronectin, integrins family, myosin, vitronectin, collagen, laminin, polyglycans, cadherin, heparin, tenascin, CD₅₄, and CAM; the compounds use for anti adhesion therapy and targeting adhesion molecules for therapy.

Applicant further states that anti adhesion therapy and targeting adhesion molecules for therapy is a new direction for development of drugs. Some examples of anti-adhesion drugs in clinical trials are Efalizumab, Odulimomab, Alicaforsen, Aselizumab etc, which target varies adhesion proteins. Please see TEXT BOOK, Adhesion Molecules: Function and Inhibition, (Reference 2), edited by Klaus Ley page 289-291, 297.

Adhesion molecules in inflammatory disease, (Reference 4), Abstract, line 7-8 “Blockade of the function of expression of CAM has emerged as a new therapeutic target in inflammatory diseases”. Applicants' invention is an anti adhesion therapy which is a new use of the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment.

In the present application, Applicants have used compounds selected from structure (2A) for anti adhesion therapy, as a mediator or inhibitor of adhesion proteins and angiopoietins, and modulation of the cell attachment, and cell adhesion.

EXPERIMENTAL DETAILS

Experiment details of herb extraction, analysis of extract components by HPLC, determination of the cell-growth activity effected by Xanifolia Y with cells derived from different human organs using MTT Assay, purification of the bioactive components from plant extract, fractionation of plant extracts with FPLC, isolation of component Ys with preparative HPLC, determination of the chemical structure, cell experiments and animal studying are disclosed in PCT/US05/31900, U.S. Ser. No. 11/289,142, U.S. Ser. No. 10/906,303, U.S. Ser. No. 11/131,551 and U.S. Ser. No. 11/683,198, filed on Mar. 7, 2007, PCT/US2007/077273, filed Aug. 30, 2007, U.S. Ser. No. 60/890,380, filed on Feb. 16, 2007, U.S. No. 60/947,705, filed on Jul. 3, 2007, PCT/US2008/002086, 1188-ALA-PCT, filed Feb. 15, 2008, App'l No. PCT/US09/34115, filed Feb. 13, 2009, the contents of which are incorporated herein by reference. Experiments 1-23 of PCT/US2008/002086, 1188-ALA-PCT, filed Feb. 15, 2008 are incorporated herein by reference.

Experiment 1 Removal of the Sugar Moiety from Saponin by Acid Hydrolysis

15 mg saponin was dissolved in 1 ml of Methanol. 1 ml of 2N HCl was then added. The mixture was refluxed in 80C water bath for 5 hours. The solution was then neutralized by adding 2 ml of 1N NaOH (to final pH 4-6). The aglycone was then extracted with ethylacetate 3 ml×2. The extracts were collected and pooled. Further isolation of aglycone (sugar-removed saponin) was achieved by HPLC with isocratic elution of 80-100% acetonitrile.

Experiment 2 Removal of the Acyl Group by Alkaline Hydrolysis Methods

20 mg of saponin was dissolved in 0.5 ml of 1N NaOH. The solution was incubated in 80C water bath for 4 hours. It was cooled to room temperature before neutralized with 0.5 ml 1N HCl (adjust pH to about 3). The mixture was extracted with 2 ml 1-butanol 3 times. The butanol fractions were collected and lyophilized. The hydrolyzed saponin with further purified with HPLC in a C-18 column eluted with 25% acetonitrile.

Experiment 3 Adding the Acyl Group to Triterpene by Esterification

Method: 40 mg of triterpene core (fraction IV) was dissolved in 1 ml pyridine in a 50 ml tube. Reaction is started by adding 0.2 ml of acyl chloride (Tigloyl chloride, angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride(senecioyl chloride), Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride or Ethylbutyryl chloride). The mixture is stirred for 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at 0C, 25C or 75C temperature. At the end of reaction, 5 ml of 2N HCl or 1M NaHCO3 is added to the reaction mixture. The solution is then extracted 3 times with 10 ml of ethyl acetate which is then evaporated under vacuum and at 45C and lyophilization. The reaction product is dissolved in 80% acetonitrile—0.005% Trifluoroacetic acid or DMSO; and was separated with HPLC. Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific reaction time. The active esterification products are purified with HPLC. The reaction product of mixtures and individual compounds are tested with MTT cytotoxic assay. See examples FIGS. 1-12

Experiment 4 Preparation of E4A

-   1. Beta-Escin dissolved in 1M NaOH (20 mg/ml) was incubated at 70C     for 5 hours. -   2. The hydrolyzed solution was neutralized with HCl and the water     was evaporated by lyophilization. -   3. The product was dissolved in 50% methanol and 1N HCl. The mixture     was incubated at 70C for 5 hours. -   4. The solution was neutralized with NaOH. -   5. The hydrolyzed product was extracted with ethylacetate, which was     subsequently removed by evaporation. -   6. Further purification of the hydrolyzed product (E4A) was archived     with FPLC chromatography in a C18 column equilibrated with 70%     acetonitrile/TFA at the flow rate of 1 ml/min.

Experiment 5 Esterification of E4A with Tigloyl Chloride

-   1. 50 mg of E4A in 1 ml pyridine, stir gently in a 50 ml tube.     Esterification was carried out at 25C by adding 200 ul Tigloyl     chloride. -   2. Stir for 1 minute; then immediately add 5 ml of 2N HCl. -   3. Stir for 1 hour and sit at room-Temp over night. -   4. Extract the esterification products with 10 ml ethylacetate. -   5. Evaporate the ethylacetate. -   6. Dissolve the sample with 1 ml DMSO. -   7. Fractionate the reaction products with HPLC. -   8. Collect samples.

Experiment 6 Isolation of E4A-Tig Active Compounds with HPLC

-   1. Column: ZORBAX ODS 9.4×250 mm, 5 um -   2. Solvents: A: 45% AN/TFA; B: 100% AN/TFA -   3. Chromatography conditions: a) Elution: Solvent A to B in 80 min;     then with solvent B for 40 min; b) flow rate: 1 ml/mim. c) Monitor     OD: at 207 nm;

Experiment 7 MTT Experiment Cells

HTB-9 (bladder), HeLa-S3 (cervix), DU145 (prostate), H460 (lung), MCF-7 (breast), K562 (leukemia), HCT116 (colon), HepG2 (liver), U2OS (bone), T98G (brain), SK-MEL-5 (Skin) and OVCAR 3, ES2 (ovary), Pancreas(Capan), Mouth(KB), Kidney(A498).

MTT Assay

The procedure for MTT assay followed the method described by Carmichael et al.(1987) with modifications. The cells were seeded into a 96-well plate at for 24 hours before drug-treatment. The cells were then exposed to the drugs for 48, 72, or 96 hours. After the drug-treatment, MTT (0.5 mg/mL) was added to cultures and incubated for an hour. The formazan (product of the reduction of tetrazolium by viable cells) formed and was dissolved with DMSO and the O.D. at 490 nm, and was measured by an ELISA reader. The MTT level of the cells before drug-treatment was also measured (T0). The % cell-growth (% G) is calculated as: % G=(TD−T0/TC−T0)×100(1), where TC or TD represents O.D. readings of control or drug-treated cells. When T0>TD, then the cytotoxicity (LC) expressed as % of the control is calculated as: % LC=(TD−TO/TO)×100(2).

Experiment 8 Chemical Synthesis, Isolation and Characterization of E4A-Tig-R

Chemical synthesis of E4A-Tig-R: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-R with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

See FIG. 23-30 See Table 1 Compound E4A-Tig-R 24,28-O-Tigloyl-3β,16α,21β,22α,24β,28-hexahydroxyolean-12-ene

Experiment 9 Chemical Synthesis, Isolation and Characterization of E4A-Tig-N

Chemical synthesis of E4A-Tig-R: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-N with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

Experiment 10 Chemical Synthesis, Isolation and Characterization of E4A-Tig-Q

Chemical synthesis of E4A-Tig-R: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-Q with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

Experiment 11 Chemical Synthesis, Isolation and Characterization of E4A-Tig-V

Chemical synthesis of E4A-Tig-V: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-V with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

Experiment 12 Chemical Synthesis, Isolation and Characterization of E4A-Tig-T

Chemical synthesis of E4A-Tig-T: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-T with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

Experiment 13 Chemical Synthesis, Isolation and Characterization of E4A-Tig-U

Chemical synthesis of E4A-Tig-S: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-S with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

Experiment 14 Chemical Synthesis, Isolation and Characterization of E4A-Tig-S

Chemical synthesis of E4A-Tig-S: 1. Preparation of E4A; 2. Esterification of E4A with Tigloyl Chloride; 3. Isolation of E4A-Tig-S with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

Experiment 15

Using method in Experiment 8, esterification of E4A with Acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, Cinnamoyl, Pentenoyl, Hexanoyl, Ethylbutyryl, gave the following compounds

Experiment 16 Esterification of E4A-Tig-N with Senecioyl Chloride

Chemical synthesis of E4A-Tig-Sen-1:1. Esterification of E4A-Tig-N with Senecioyl Chloride; 3. Isolation of E4A-Tig-Sen-1 with HPLC Cytotoxic activity determination: 1. MTT assay Chemical structure determination: 1. NMR analysis; 2. Mass Spectrum analysis

Experiment 17

Esterification of E4A-Tig-N with angeloyl chloride, Acetyl chloride, Crotonoyl chloride, 3,3-Dimethylartyloyl chloride, senecioyl chloride, Cinnamoyl chloride, Pentenoyl chloride, Hexanoyl chloride, benzoyl chloride or Ethylbutyryl chloride; Isolation with HPLC; Cytotoxic activity determination; Chemical structure determination with the method of Experiment 8, gave the following compounds:

Experiment 18 Inhibition of Cell Adhesion

Methods and Results. ES2 or Hey8A cells were plated in T25 flasks with medium containing 5 ug/ml of compounds selected from structure (2A) including E4A-Tig-R, E4A-Tig-V, E4A-Tig-S, E4A-Tig-N, E4A-Tig-Q, E4A-Tig-T. Cultures were incubated for 5 hours. Attached cells were removed from flasks by trypsinization and the amounts were counted. Compare to no drug controls, 80±4% of ES2 cells and 60±4% of Hey8A cells were found attached to flasks under this condition. At 5 ug/ml of above compounds, over 90% of unattached cells are alive as determined by the trypan Blue exclusion assay and by their ability to re-attach to flasks when plating in medium without tested compounds. However, with 10 ug/ml tested compounds, less than 40% of cells attached to flasks and many of them are dead cells. This experiment shows that tested compounds inhibit cells adhesion process.

Experiment 19 Fibronectin Secretion Experiment

Western blot is applied in this invention as a method to detect the specific proteins in treated and untreated cells with compounds in this invention, wherein the cells are bladder, cervix, prostate, lung, breast, leukemia, colon, liver, bone, brain, Skin, ovary, Pancreas(Capan), Mouth(KB), Kidney

Cells: targeted cells were grown in RPMI 1640 medium. 1.5 million cells were seeded in a T25 flask and grown for 24 hours before drug-treatment.

Drug-treatment: Cells cultures were replaced with fresh RPMI medium containing either 2.5 ul of DMSO (as control) [D]; or 10, 20, 30, 40, 80 ug/ml of tested compounds. After 24 hours, aliquot of culture medium was taken out for Fibronectin determination (Western blot method).

Cell viability at 24 hours was determined by MTT assay. Cultures were replaced with RPMI medium (5 ml) with MTT and incubated for an hour. The formation of formazan was dissolved in 10 ml of DMSO and OD at 570 nm was measured (MTT units). Western Blot Spent culture medium was mixed with SDS sample buffer, boiled for 3 minutes before loading to SDS gel. Samples were applied to a 6-10% SDS gel and electrophoresis was conducted with 100 volts for 2 hours. Protein was transferred to a nitrocellulose membrane electrophoretically. The nitrocellulose blot was incubated with the first antibody and second antibody (AP conjugated, Promega S3721). The immuno-bands were developed with BCIP/NBT color development system.

Determination of Western band intensity: The band-images of Western blot were captured with a digital camera and the intensity of bands was determined using “Image J” software.

Results show that compounds of E4A-Tig-R, E4A-Tig-V, E4A-Tig-S, E4A-Tig-N, E4A-Tig-Q, E4A-Tig-T inhibit fibronectin secretion from 20-40%.in bladder, cervix, prostate, lung, breast, leukemia, colon, liver, bone, brain, Skin, ovary, Pancreas(Capan), Mouth(KB), Kidney.

TABLE 1 Table. ¹³C and ¹H NMR data for E4A-Tig-R (in DMSO-d₆)^(a) Position C H Key HMBC correlations 1 38.24 0.96, t, 1.56, t C-25 2 26.77 1.52, br, m — 3 76.69 3.15, 1H, dd C23, C24 4 41.5 — — 5 54.88 0.82, 1H C23, C24, C25 6 19.51 1.47, 1.65, C5 7 32.81 1.28, 1.43 C26 8 39 — C27, C26 9 46.1 1.55 m C25, C26 10 36.33 — C9, C25, C26 11 22.97 1.79 m C9 12 122.25 5.18, 1H, t C9, C11, C14, C18 13 142.32 — C18, C27 14 40.7 — C26, C27 15 33.56 1.28, 1.64 C27 16 66.47 4.01, 1H, s C22, C28 17 45.3 — C22, C28 18 39.9 2.41, br, m, C12, C28 19 46.59 0.98, 2.42 m C29, C30 20 35.23 — C29, C30 21 76.50 3.84, 1H, d, 9.6 Hz C22, C29, C30 22 71.89 3.55, 1H, d, 9.6 Hz C21, C28, 23 22.62 1.06, 3H, s C3, C5, C24, 24 66.17 4.14, 1H, d, 12 Hz C3, C5, C-23 4.17, 1H, d, 12 Hz 24-O-Tig-C1′ 25 14.89 0.88, 3H, s C-1, C-5, C-9, C-10 26 16.13 0.81, 3H, s C-7, C-8, C-9, C-14 27 26.65 1.36, 3H, s C-8, C-18, C14, C-15 28 65.34 3.68, 1H, d, 10.4 Hz, C17, C-18, C-22 3.73, 1H, d, 10.4 Hz, 28-O-Tig C1′ 29 29.87 0.86, 3H, s C-19, C20, C-21, C-30 30 18.49 0.85, 3H, s C-19, C20, C-21, C-29 24-O-Tig 1′ 167.24 — C24, Tig C-3′, 2′ 128.29 — Tig-C3′, Tig C-4′, Tig C-5′ 3′ 136.8 6.77, 1H, Tig C-4′, Tig C-5′ 4′ 11.9 1.78, 3H, Tig C-1′, C-2′, C-3′ 5′ 13.99 1.77, 3H, Tig C-1′, C-2′, C-3′ 28-O-Tig 1′ 166.68 — C28, Tig C-3′ 2′ 128.1 — Tig C-3′, Tig C-4′, Tig C-5′ 3′ 136.5 6.77, 1H, Tig C-4′, Tig C-5′ 4′ 11.9 1.78, 3H, Tig C-1′, C-2′, C-3′ 5′ 14.08 1.77, 3H, Tig C-1′, C-2′, C-3′

TABLE 2 Table. ¹³C and ¹H NMR data for E4A-Tig-V (in DMSO-d₆)^(a) Position C H Key HMBC correlations 1 38.20 0.98, 1.57 C-25 2 26.75 1.54, br, m — 3 76.65 3.15, 1H, dd C23, C24 4 41.48 — — 5 54.82 0.82, 1H C23, C24, C25 6 19.49 1.47, 1.65, C5 7 32.71 1.29, 1.46 C26 8 39 — C27, C26 9 46.09 1.57 m C25, C26 10 36.31 — C5, C9, C25, 11 22.97 1.81 m 12 122.65 5.22, 1H, t C9, C11, C14, C18 13 141.83 — C18, C19, C27 14 40.68 — C12, C18, C26, C27 15 33.59 1.29, 1.66 C27 16 66.14 4.03, 1H, s C18, C22, C28 17 45.69 — C18, C22, C28 18 39.5 2.5, br, m, C12, C19, C28 19 46.17 1.07, 2.56 m C18, C29, C30 20 35.33 — C29, C30 21 79.74 5.57 1H, d, 9.6 Hz C20, C22, C29, C30 21-O-Tig-C1, 22 69.39 3.79, 1H, d, 9.6 Hz C21, C28, 23 22.60 1.06, 3H, s C3, C4, C5, C24, 24 66.14 4.15 (dd 16.8, 12 Hz) C3, C4, C5, C-23 24-O-Tig-C1′ 25 14.87 0.88, 3H, s C-1, C-5, C-9, C-10 26 16.09 0.81, 3H, s C-7, C-8, C-9, C-14 27 26.7 1.38, 3H, s C-8, C13, C14, C-15 28 65.09 3.72 (dd 28.4, 10.4) C16, C17, C-18, C-22 28-O-Tig C1′ 29 29.24 0.74, 3H, s C-19, C20, C-21, C-30 30 19.35 0.98, 3H, s C-19, C20, C-21, C-29 21-O-Tig 1′ 167.05 — C21, Tig C-3′, 2′ 128.04 — Tig-C3′, Tig C-4′, Tig C-5′ 3′ 135.61 6.77, 1H, Tig C-4′, Tig C-5′ 4′ 11.94 1.79, br, m, 3H, Tig C-1′, C-2′, C-3′ 5′ 13.84 1.78, br, m, 3H, Tig C-1′, C-2′, C-3′ 24-O-Tig 1′ 167.26 — C24, Tig C-3′ 2′ 128.26 — Tig C-3′, Tig C-4′, Tig C-5′ 3′ 136.60 6.77, 1H, Tig C-4′, Tig C-5′ 4′ 11.94 1.79, br, m, 3H, Tig C-1′, C-2′, C-3′ 5′ 13.96 1.78, br, m, 3H, Tig C-1′, C-2′, C-3′ 28-O-Tig 1′ 166.64 — C28, Tig C-3′ 2′ 128.71 — Tig C-3′, Tig C-4′, Tig C-5′ 3′ 136.96 6.77, 1H, Tig C-4′, Tig C-5′ 4′ 12.09 1.79, br, m, 3H, Tig C-1′, C-2′, C-3′ 5′ 14.06 1.78, br, m, 3H, Tig C-1′, C-2′, C-3′ 

1-17. (canceled)
 18. A compound selected from the structure:

R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14, R15 are independently selected from the group of hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-Ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, D-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl, CH3, CH2OH, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, D-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, alkane, alkene and sugar moiety or derivatives thereof; wherein the structure (2A) comprises at least 2 groups selected from O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; or wherein R1 and R2 are selected from O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl; or wherein wherein the R1 and R2 are attached OH; or wherein R4, R10 are attached a CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, or CH2O-ethylbutyryl; wherein the R3 and R8 is hydrogen or hydroxyl; wherein the R9, R11, R12, R13, R14, R15 are independently attached with a methyl; wherein R3 is H, OH or absent; wherein R8 is H or OH; wherein R16 is H, CH3, OH, or R4 and R16 may together form —CH2—X—, CH(OH)—X— or C(═O)—X—, wherein the —X— may be O or NH or S; wherein when the C12-13 of ring 3 of the triterpene has a double bond then R16 is absent; or wherein R10 is CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, or CH2O-ethylbutyryl; R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14 or R15 comprise of one or more acids or at least 1, or 2, or 3, or 4 of R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14 and R15 is hydroxyl; or at least 2, or 3, or 4, or 5, or 6, or 7 of R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14 and R15 are independently attached a group selected from the group of O-acetyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, alkane, alkene and derivatives thereof, wherein the group is attached to the triterpene directly or by connecting moiety(ies); wherein R10 and at least 1 or 2, or 3, or 4, or 5, or 6, or 7 of R1, R2, R3, R4, R5, and R8 are independently attached a group selected from the group of O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl, CH3, CH2OH, O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, and derivatives thereof,
 19. The compound of claim 18 having the structure:

wherein R1, R2, R3, R4, R5, R8, R9, R10, R11, R12, R13, R14, R15 are independently selected from the group of CH3, CH2OH, hydrogen, hydroxyl, methyl, O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl,alkane, alkene and sugar moiety or acid thereof; wherein R10 and any 1 or 2 or 3 or 4 of R1, R2, R3, R4, R5, and R8 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl or wherein R1, R2, are independently attached an OH-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl; R9, R11, R12, R13, R14, R15 are independently attached a CH3; or wherein R10 is attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, D-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl; or wherein R4 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl; wherein R3 is OH or H or absent; wherein R1, R2, R3, R5, R8 are OH or H or absent; wherein R9, R11, R12, R13, R14, and R15 are CH3; or wherein R1, R2, R5, R8 represent OH; R3 represents OH, H or absent; R4, R10 represent CH2Oangeloyl; R9, R11, R12, R13, R14, R15 represent CH3; or wherein R1, R2, R5, R8 represent OH or O-tigloyl; R3 represents OH, H, or absent; R4, R10 represent CH2O tigloyl; R9, R11, R12, R13, R14, R15 represent CH3; wherein the group attaching to the core compound selected from acetyl, angeloyl, tigloyl, senecioyl, Crotonoyl, O-3,3-Dimethylartyloyl, Cinnamoyl, Pentenoyl, Hexanoyl, benzoyl, Ethylbutyryl, alkyl, dibenzoyl, benzoyl, methylbutanoyl, methylpropanoyl, alkanoyl, alkenoyl, benzoyl alkyl substituted alkanoyl, alkanoyl substituted phenyl, alkenoyl substituted phenyl, aryl, acyl, heterocylic, heteroraryl and alkenylcarbonyl are interchangeable; wherein the attached group(s) is/are selected in combination thereof.
 20. The compound of claim 18, wherein R10 and at least or 2 of R1, R2, R3, R4, R5, R8, are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl.
 21. The compound of claim 18, wherein R1, R4 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl.
 22. The compound of claim 18, wherein R4 and R10 are independently attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl.
 23. The compound of claim 18, wherein R10 is attached an O-angeloyl, O-tigloyl, O-senecioyl, O-acetyl, O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-Hexanoyl, O-benzoyl, O-ethylbutyryl,O-alkyl, O-dibenzoyl, O-benzoyl, O-alkanoyl, O-alkenoyl, O-benzoyl alkyl substituted O-alkanoyl, O-alkanoyl substituted phenyl, O-alkenoyl substituted phenyl, O-aryl, O-acyl, O-heterocylic, O-heteroraryl, O-alkenylcarbonyl, CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-Pentenoyl, CH2O-Hexanoyl, CH2O-benzoyl, CH2O-Ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl.
 24. The compound of claim 18, wherein R4 and R10 are independently attached an CH2O-angeloyl, CH2O-tigloyl, CH2O-senecioyl, CH2O-acetyl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl, CH2O-alkyl, CH2O-dibenzoyl, CH2O-benzoyl, CH2O-alkanoyl, CH2O-alkenoyl, CH2O-benzoyl alkyl substituted O-alkanoyl, CH2O-alkanoyl substituted phenyl, CH2O-alkenoyl substituted phenyl, CH2O-aryl, CH2O-acyl, CH2O-heterocylic, CH2O-heteroraryl, CH2O-alkenylcarbonyl; wherein R1, R2, R3, R5, R8 are OH or H or absent; wherein R9, R11, R12, R13, R14, and R15 are CH3.
 25. The compound of claim 18, wherein any 2 of R1, R2, R3, R4, R5, R8, are independently attached an O-crotonoyl, O-3,3-dimethylartyloyl, O-cinnamoyl, O-pentenoyl, O-hexanoyl, O-benzoyl, O-ethylbutyryl, CH2O-crotonoyl, CH2O-3,3-dimethylartyloyl, CH2O-cinnamoyl, CH2O-pentenoyl, CH2O-hexanoyl, CH2O-benzoyl, CH2O-ethylbutyryl.
 26. The compound of claim 18, wherein the compound is selected from the following: a) An isolated, purified or synthesized compound having structure:

or chemical name: 24,28-O-Tigloyl-3β,16α,21β,22α,24β,28-hexahydroxyolean-12-ene, b) An isolated, purified or synthesized compound having structure:

or chemical name: 24-O-Tigloyl-3β,16α,21β,22α,24β,28-hexahydroxyolean-12-ene, c) An isolated, purified or synthesized compound having structure:

or chemical name: 22,28-O-Tigloyl-3β,16α,21β,22α,24β,28-hexahydroxyolean-12-ene, d) An isolated, purified or synthesized compound having structure:

or chemical name: 21,24,28-O-Tigloyl-3β,16α,21β,22α,24β,28-hexahydroxyolean-12-ene, e) An isolated, purified or synthesized compound having structure:

or chemical name: 22,24,28-O-Tigloyl-3β,16α, 21β,22α,24β,28-hexahydroxyolean-12-ene, f) An isolated, purified or synthesized compound having structure:

or chemical name: 3,21,28-O-Tigloyl-3β,16α,21β,22α,24β, 28-hexahydroxyolean-12-ene, g) An isolated, purified or synthesized compound having structure:

or chemical name: 21,24-O-Tigloyl-3β,16α,21β,22α,24β,28-hexahydroxyolean-12-ene.
 27. The composition comprises compound of claim 18, further comprising a pharmaceutically acceptable carrier or diluent.
 28. The compound of claim 18, wherein the compound for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, wherein the cancer is selected from the group of breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells is selected from the group of breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell.
 29. The compound of claim 18, wherein the compound for treating cancers, inhibition of cancer growth, cancer invasion, cells invasion, cancer cell invasion; cell adhesion, cell attachment, cell circulating; for inhibiting viruses; for preventing cerebral aging; for improving memory; improving cerebral functions; for curing enuresis, frequent micturition, urinary incontinence; dementia, Alzheimer's disease, autism, brain trauma, Parkinson's disease or other diseases caused by cerebral dysfunctions; for treating arthritis, rheumatism, poor circulation, arteriosclerosis, Raynaud's syndrome, angina pectoris, cardiac disorder, coronary heart disease, headache, dizziness, kidney disorder; cerebrovascular disease; inhibiting NF-Kappa B activation; for treating brain edema, severe acute respiratory syndrome, respiratory viral diseases, chronic venous insufficiency, hypertension, chronic venous disease, oedema, inflammation, hemonhoids, peripheral edema formation, varicose vein disease, flu, post traumatic edema and postoperative swelling; for inhibiting blood clots, for inhibiting ethanol absorption; for lowering blood sugar; for regulating adrenocorticotropin and corticosterone levels. This invention provides a composition for AntiMS, antianeurysm, antiasthmatic, anti-oedematous, anti-inflammatory, antibradykinic, anticapillarihemorrhagic, anticephalagic, anticervicobrachialgic, antieclamptic, antiedemic, antiencaphalitic, antiepiglottitic, antiexudative, antiflu, antifracture, antigingivitic, antihematomic, antiherpetic, antihistaminic, antihydrathritic, antimeningitic, antioxidant, antiperiodontic, antiphlebitic, antipleuritic, antiraucedo, antirhinitic, antitonsilitic, antiulcer, antivaricose, antivertiginous, cancerostatic, corticosterogenic, diuretic, fungicide, hemolytic, hyaluronidase inhibitor, lymphagogue, natriuretic, pesticide, pituitary stimulant, thymolytic, vasoprotective, inhibiting leishmaniases, modulating adhesion or angiogenesis of cells, antiparasitic; increase the expression of the genes: ANGPT2, DDIT3, LIF and NFKB1Z, and manufacturing an adjuvant composition and venotonic treatment.
 30. The compound of claim 18, wherein the compound for anti-adhesion therapy.
 31. A composition comprising an effective amount of compound of claim 18 as a medicament.
 32. The compound of claim 18, wherein the compound can be obtained with the method:
 1. Dissolving core compound or triterpenes, hydroxylated triterpenes core in pyridine
 2. Adding acyl chloride
 3. The mixture is stirred for length of time including 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at different temperature
 4. At the end of reaction, an aqueous solution of acid or base, or water is added to the reaction mixture.
 5. The solution is then extracted of ethyl acetate and lyophilization.
 6. Dissolving the reaction product in acetonitrile with Trifluoroacetic acid or DMSO.
 7. Testing the reaction product of mixtures and individual fractions with MTT cytotoxic assay.
 8. Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific reaction time.
 9. Purifiing the active esterification products with HPLC.
 10. Collecting the products.
 11. Testing the products.
 33. The compound of claim 32, wherein the core compound is terpene, isoprene, or triterpene core; wherein the core compound is hydroxylated; wherein the core compound was dissolved in pyridine; wherein the acyl chloride including tigloyl chloride, angeloyl chloride, acetyl chloride, crotonoyl chloride, 3,3-dimethylartyloyl chloride, senecioyl chloride, cinnamoyl chloride, pentenoyl chloride, hexanoyl chloride, benzoyl chloride and ethylbutyryl chloride; wherein the reaction time for the mixture is stirred for 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days; wherein the temperature is 0C, 25C, 50C or 75C temperature; wherein the acid including HCl or the base is a weak base including NaHCO3 is added to the reaction mixture; wherein the solution is then extracted 3 times with ethyl acetate and lyophilization; wherein the reaction product is dissolved in 80% acetonitrile—0.005% Trifluoroacetic acid or DMSO; wherein selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a reaction time of 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days.
 34. The compound of claim 18, wherein the said compound is present in a concentration of 0.01 ug/ml to 40 ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 0.01 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 0.1 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 1 ug/ml to 30 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 3 ug/ml to 30 ug/ml; or present in a concentration of 4 ug/ml to 5 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 7.5 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 4 ug/ml to 30 ug/ml, or present in a concentration of 5 ug/ml to 8 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 9 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 5 ug/ml to 30 ug/ml, or present in a concentration of 7 ug/ml to 8 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 9 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 10 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 15 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 20 ug/ml, or wherein said compound is present in a concentration of 7 ug/ml to 30 ug/ml; or wherein administration is by intravenous drip: 0.003-0.03 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.003-0.03 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution, or 0.01-0.03 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.01-0.03 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution, or 0.01-0.05 mg/kg body weight of compound dissolved in 250 ml of 10% glucose solution or in 250 ml of 0.9% NaCl solution, or by intravenous injection: 0.01-0.05 mg/kg body weight per day of compound dissolved in 10-20 ml of 10% glucose solution or of 0.9% NaCl solution.
 35. A method for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, wherein the cancer is selected from the group of breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells is selected from the group of breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell, comprising administering to said subject an effective amount of compound selected from claim
 17. 36. A method for treating cancer, inhibiting cancer growth, inhibiting cancer invasion, inhibiting cancer metastasis, modulating cell adhesion, modulating cell attachment, wherein the cancer is selected from the group of breast cancer, leukocytic cancer, liver cancer, ovarian cancer, bladder cancer, prostatic cancer, skin cancer, bone cancer, brain cancer, leukemia cancer, lung cancer, colon cancer, CNS cancer, melanoma cancer, renal cancer, cervical cancer, esophageal cancer, testicular cancer, spleenic cancer, kidney cancer, lymphhatic cancer, pancreatic cancer, stomach cancer and thyroid cancer; wherein the cells is selected from the group of breast cell, leukocytic cell, liver cell, ovarian cell, bladder cell, prostatic cell, skin cell, bone cell, brain cell, leukemia cell, lung cell, colon cell, CNS cell, melanoma cell, renal cell, cervical cell, esophageal cell, testicular cell, spleenic cell, kidney cell, lymphhatic cell, pancreatic cell, stomach cell and thyroid cell, comprising administering to said subject an effective amount of compound selected from claim
 25. 37. A method for synthesizing an active compound or triterpene, wherein the compound or triterpene is attached one or more of the functional group selected from the group of angeloyl, tigloyl, senecioyl, acetyl, crotonoyl, dimethylartyloyl, cinnamoyl, pentenoyl, hexanoyl, benzoyl, ethylbutyryl, alkyl and phenyl; wherein the method comprises following steps:
 1. Dissolving core compound, triterpenes, hydroxylated triterpenes core in pyridine
 2. Adding the functional group or acyl chloride.
 3. The mixture is stirred for length of time including 5 sec, 1 min, 2 min, 5 min, 10 min, 30 min, 1 hr, 2 hr, 18 hr, 2 days or 3 days at different temperature
 4. At the end of reaction, an aqueous solution of acid or base, or water is added to the reaction mixture.
 5. The solution is then extracted of ethyl acetate and lyophilization.
 6. Dissolving the reaction product in acetonitrile with Trifluoroacetic acid or DMSO.
 7. Testing the reaction product of mixtures and individual fractions with MTT cytotoxic assay.
 8. Selecting the HPLC fractions for isolation is according to the cytotoxic activity of the reaction product obtained at a specific reaction time.
 9. Purifiing the active esterification products with HPLC.
 10. Collecting the products.
 11. Testing the products. 